SECOND SUPPLEMENTAL INDENTURE

Exhibit 4.3

SECOND SUPPLEMENTAL INDENTURE

Dated as of June 9, 2009

Supplementing that Certain

INDENTURE

Dated as of June 9, 2009

Among

EXPRESS SCRIPTS, INC.,

THE GUARANTORS PARTIES HERETO

and

UNION BANK, N.A.,

as Trustee

6.250% SENIOR NOTES DUE 2014

TABLE OF CONTENTS

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          This Second Supplemental Indenture, dated as of June 9, 2009 (the “ Second Supplemental Indenture ”), among Express Scripts, Inc., a corporation duly organized and existing under the laws of the State of Delaware, having its principal office at One Express Way, St. Louis, Missouri (herein called the “ Company ”), the Guarantors party hereto and Union Bank, N.A., a national banking association, as Trustee hereunder (herein called the “ Trustee ”), supplements that certain Indenture, dated as of June 9, 2009, among the Company, the Guarantors and the Trustee (the “ Indenture ”).

RECITALS OF THE COMPANY

          A. The Company has duly authorized the execution and delivery of the Indenture to provide for the issuance from time to time of its unsecured debentures, notes, or other evidences of indebtedness to be issued in one or more series as provided for in the Indenture.

          B. Each of the Guarantors has duly authorized the execution and delivery of the Indenture and the Guarantees, the form of which is attached hereto, in order to fully and unconditionally guarantee the Company’s obligations under the Indenture.

          C. The Indenture provides that the Securities of each series shall be in substantially the form set forth in the Indenture, or in such other form as may be established by or pursuant to a Board Resolution or in one or more supplemental indentures thereto, in each case with such appropriate insertions, omissions, substitutions, and other variations as are required or permitted by the Indenture, and may have such letters, numbers, or other marks of identification and such legends or endorsements placed thereon as may be required to comply with the rules of any securities exchange or Depositary therefor or as may, consistently therewith, be determined by the officers executing such Securities, as evidenced by their execution thereof.

          D. The Company and the Trustee have agreed that the Company shall issue and deliver, and the Trustee shall authenticate, Securities denominated “6.250% Senior Notes due 2014” pursuant to the terms of this Second Supplemental Indenture and substantially in the form set forth in Section 3.2 below, in each case with such appropriate insertions, omissions, substitutions, and other variations as are required or permitted by the Indenture and this Second Supplemental Indenture, and with such letters, numbers, or other marks of identification and such legends or endorsements placed thereon as may be required to comply with the rules of any securities exchange or Depositary therefor or as may, consistently herewith, be determined by the officers executing such Notes, as evidenced by their execution of such Notes.

ARTICLE I

Issuance of Securities

          SECTION 1.1. Issuance of Notes; Principal Amount; Maturity; Title.

          (1) On June 9, 2009, the Company shall issue and deliver to the Trustee, and the Trustee shall authenticate, the Initial Notes substantially in the form set forth in

Section 3.2 below, in each case with such appropriate insertions, omissions, substitutions and other variations as are required or permitted by the Indenture and this Second Supplemental Indenture, and with such letters, numbers, or other marks of identification and such legends or endorsements placed thereon as may be required to comply with the rules of any securities exchange or Depositary therefor or as may, consistently herewith, be determined by the officers executing such Notes, as evidenced by their execution of such Notes.

          (2) The Initial Notes to be issued pursuant to this Second Supplemental Indenture shall be issued in the aggregate principal amount of $1,000,000,000 and shall mature on June 15, 2014 unless the Notes are redeemed prior to that date as described in Section 5.1 and 5.3. The aggregate principal amount of Initial Notes Outstanding at any time may not exceed $1,000,000,000, except for Notes issued, authenticated and delivered upon registration of transfer of, or in exchange for, or in lieu of, other Notes of the Series pursuant to Sections 304, 305, 306, 906 or 1107 of the Indenture and except for any Notes which, pursuant to Section 303 of the Indenture, are deemed never to have been authenticated and delivered. The Company may without the consent of the Holders, issue additional notes hereunder as part of the same series and on the same terms and conditions (and having the same Guarantors) and with the same CUSIP numbers as the Initial Notes (“Additional Notes”); provided that if any Additional Notes are issued at a price that causes such Additional Notes to have “original issue discount” within the meaning of Section 1273 of the United States Internal Revenue Code of 1986, as amended, and regulations of the United States Department of Treasury thereunder (the “ Code ”), such Additional Notes shall not have the same CUSIP number as the Initial Notes.

          (3) The Notes shall be issued only in fully registered form without coupons in minimum denominations of $2,000 and any integral multiple of $1,000.

          (4) Pursuant to the terms hereof and Section 301 of the Indenture, the Company hereby creates a series of Securities designated as the “6.250% Notes due 2014” of the Company (as amended or supplemented from time to time, that are issued under this Second Supplemental Indenture, including both the Initial Notes and the Additional Notes, if any, the “ Notes ”), which Notes shall be deemed “Securities” for all purposes under the Indenture.

          SECTION 1.2. Interest.

          (1) Interest on a Note will accrue at the per annum rate of 6.250% (the “ Note Interest Rate ”), from and including the date specified on the face of such Note until the principal thereof is paid, deemed paid, or made available for payment and, in each case, will be paid on the basis of a 360-day year comprised of twelve 30-day months.

          (2) The Company shall pay interest on the Notes semi-annually in arrears on June 15 and December 15 of each year (each, an “ Interest Payment Date ”), commencing December 15, 2009.

          (3) Interest shall be paid on each Interest Payment Date to the registered Holders of the Notes after the close of business on the Regular Record Date.

          (4) Amounts due on the Maturity Date or earlier Redemption Date of the Notes will be payable at the corporate trust office of the Trustee at 551 Madison Avenue, 11th Floor, New York, NY 10022. The Company may make payment of interest on an Interest Payment Date in respect of Notes in certificated form by check mailed to the address of the Person entitled to the payment as it appears in the Security Register or by transfer to an account maintained by the payee with a bank located in the United States. The Company shall make payments of principal, premium, if any, and interest in respect of Notes in book-entry form to DTC in immediately available funds, while disbursement of such payments to owners of beneficial interests in Notes in book-entry form will be made in accordance with the procedures of DTC and its participants in effect from time to time.

          (5) Neither the Company nor the Trustee shall impose any service charge for any transfer or exchange of a Note. However, the Company may ask Holders of the Notes to pay any taxes or other governmental charges in connection with a transfer or exchange of Notes.

          (6) If any Interest Payment Date, Stated Maturity Date or Redemption Date falls on a day that is not a Business Day in the City of New York, the Company will make the required payment of principal, premium, if any, and/or interest on the next succeeding Business Day as if it were made on the date payment was due, and no interest will accrue on the amount so payable for the period from and after that Interest Payment Date, the Stated Maturity Date or earlier Redemption Date, as the case may be, to such next succeeding Business Day.

          SECTION 1.3. Relationship with Indenture.

          The terms and provisions contained in the Indenture will constitute, and are hereby expressly made, a part of this Second Supplemental Indenture. However, to the extent any provision of the Indenture conflicts with the express provisions of this Second Supplemental Indenture, the provisions of this Second Supplemental Indenture will govern and be controlling.

ARTICLE II

Definitions and Other Provisions of General Application

          SECTION 2.1. Definitions.

          The terms defined in this Section 2.1 (except as herein otherwise expressly provided or unless the context of this Second Supplemental Indenture otherwise requires) for all purposes of this Second Supplemental Indenture and of any indenture supplemental hereto have the respective meanings specified in this Section 2.1. All other terms used in this Second Supplemental Indenture that are defined in the Indenture or the Trust Indenture Act, either directly or by reference therein (except as herein otherwise

expressly provided or unless the context of this Second Supplemental Indenture otherwise requires), have the respective meanings assigned to such terms in the Indenture or the Trust Indenture Act, as the case may be, as in force at the date of this Second Supplemental Indenture as originally executed; provided that any term that is defined in both the Indenture and this Second Supplemental Indenture shall have the meaning assigned to such term in this Second Supplemental Indenture.

          “ 2012 Notes Supplemental Indenture ” means the First Supplemental Indenture, dated as of June 9, 2009, among the Company, the Guarantors and the Trustee related to the 2012 Notes.

          “ 2012 Notes ” means the 5.250% Senior Notes due 2012 as amended or supplemented from time to time, that are issued under the 2012 Notes Supplemental Indenture.

          “ 2019 Notes Supplemental Indenture ” means the Third Supplemental Indenture, dated as of June 9, 2009, among the Company, the Guarantors and the Trustee related to the 2019 Notes.

          “ 2019 Notes ” means the 7.250% Senior Notes due 2019 as amended or supplemented from time to time, that are issued under the 2019 Notes Supplemental Indenture.

          “ Acquisition ” means the acquisition of the Pharmacy Benefit Management Business of WellPoint, Inc., including all of the shares and equity interest of the Target Companies by the Company as contemplated by the Acquisition Agreement.

          “ Acquisition Agreement ” means the Stock and Interest Purchase Agreement between the Company and WellPoint, Inc., dated April 9, 2009.

          “ Additional Notes ” has the meaning specified in Section 1.1(2).

          “ Affiliate ” of any specified Person means any other Person directly or indirectly controlling or controlled by or under direct or indirect common control with such specified Person. For the purposes of this definition, “control” when used with respect to any specified Person means the power to direct the management and policies of such Person, directly or indirectly, whether through the ownership of voting securities, by contract or otherwise; and the terms “controlling” and “controlled” have meanings correlative to the foregoing.

          “ Applicable Procedures ” means, with respect to any transfer or transaction involving a Global Security or beneficial interest therein, the rules and procedures of DTC, Euroclear and Clearstream, in each case to the extent applicable to such transaction and as in effect from time to time.

          “ Applied Amounts ” means an amount (which may be conclusively determined by the Board of Directors) equal to the greater of (i) capitalized rent with respect to the applicable machinery and/or equipment and (ii) the fair value of the

applicable machinery and/or equipment, that is applied within 180 days of the applicable transaction or transactions to repayment of the Notes or to the repayment of any Indebtedness which, in accordance with GAAP, is classified as long-term debt and that is on parity with the Notes.

          “ Below Investment Grade Rating Event ” means the Notes are not rated, or are rated below an Investment Grade Rating by each of the Rating Agencies on any date during the period commencing 60 days prior to the public notice of an arrangement that could result in a Change of Control until the end of the 60-day period following public notice of the occurrence of the Change of Control (which 60-day period shall be extended so long as the rating of the Notes is under publicly announced consideration for possible downgrade by either of the Rating Agencies); provided that a Below Investment Grade Rating Event otherwise arising by virtue of a particular reduction in, or termination of, any rating shall not be deemed to have occurred in respect to a particular Change of Control (and thus shall not be deemed a Below Investment Grade Rating Event for purposes of a Change of Control Triggering Event) if the Rating Agency or Rating Agencies ceasing to rate the Notes or making the reduction in rating to which this definition would otherwise apply do not announce or publicly confirm or inform the Trustee in writing at its request that the termination or reduction was the result, in whole or in part, of any event or circumstance comprised of or arising as a result of, or in respect of, the applicable Change of Control (whether or not the applicable Change of Control shall have occurred at the time of the Below Investment Grade Rating Event).

          “ Beneficial Owner ” shall mean any Person who is considered a beneficial owner of a security for purposes of Rule 13d-3 promulgated of the Exchange Act.

          “ Bridge Loan ” means the proposed bridge financing to be used to finance the Acquisition incurred on or prior to the date of the Acquisition.

          “ Capital Stock ” of any Person means any and all shares, interests, participations or other equivalents (however designated) of capital stock of such Person and all warrants or options to acquire such capital stock.

          “ Change of Control Offer ” has the meaning specified in Section 6.3(1).

          “ Change of Control Payment ” has the meaning specified in Section 6.3(1).

           “Change of Control Payment Date” has the meaning specified in Section 6.3(2)(iii).

          “ Change of Control Triggering Event ” means the occurrence of both a Change of Control and a Below Investment Grade Rating Event.

          “ Change of Control ” means the occurrence of any of the following: (1) the direct or indirect sale, transfer, conveyance or other disposition (other than by way of merger or consolidation), in one or a series of related transactions, of all or substantially all of the properties and assets of the Company and its Subsidiaries taken as a whole to any Person or Group other than the Company or one of its Subsidiaries; (2) the approval

by the holders of the Company’s Common Stock of any plan or proposal for the liquidation or dissolution of the Company (whether or not otherwise in compliance with the provisions of this Second Supplemental Indenture and the Indenture); (3) the consummation of any transaction (including any merger or consolidation) the result of which is that any Person or Group becomes the Beneficial Owner directly or indirectly, of more than 50% of the then outstanding number of shares of the Company’s Voting Stock; (4) the Company consolidates with or merges with or into any Person, or any Person consolidates with, or mergers with or into, the Company, pursuant to a transaction in which any of the outstanding Voting Stock of the Company or such other Person is converted into or exchanged for cash, securities or other property (except when Voting Stock of the Company is converted into, or exchanged for, at least a majority of the Voting Stock of the surviving Person immediately after giving effect to the transaction); or (5) the first day on which a majority of the members of the Company’s Board of Directors are not Continuing Directors.

          “ Clearstream ” means Clearstream Banking, S.A.

          “ Code ” has the meaning specified in Section 1.1(2).

          “ Common Stock ” shall mean shares of the Company’s Common Stock, $0.01 par value per share, as they exist on the date of this Second Supplemental Indenture or any other shares of Capital Stock of the Company into which the Common Stock shall be reclassified or changed.

          “ Comparable Treasury Issue ” means the United States Treasury security or securities selected by an Independent Investment Banker as having an actual or interpolated maturity comparable to the remaining term of the Notes being redeemed that would be utilized, at the time of selection and in accordance with customary financial practice, in pricing new issues of corporate debt securities of a comparable maturity to the remaining term of such Notes.

          “ Comparable Treasury Price ” means with respect to any Redemption Date: (i) the average of three Reference Treasury Dealer Quotations for the Redemption Date, after excluding the highest and lowest such Reference Treasury Dealer Quotations, or (ii) if the Trustee obtains fewer than four Reference Treasury Dealer Quotations, the average of all Reference Treasury Dealer Quotations for the Redemption Date so obtained.

          “ Consolidated Net Worth ” means, at any date, the sum of all amounts which would be included under stockholders’ equity on a consolidated balance sheet of the Company and its Subsidiaries determined in accordance with GAAP on such date or, in the event such date is not a fiscal quarter end, as of the immediately preceding fiscal quarter end.

          “ Continuing Directors ” means, as of any date of determination, any member of the Company’s Board of Directors who (1) was a member of the Board of Directors on the date of the issuance of the Initial Notes; or (2) was nominated for

election or elected to the Board of Directors with the approval of at least a majority of the Continuing Directors who were members of the Board of Directors at the time of such nomination or election (either by a specific vote or by approval of the Company’s proxy statement in which such member was named as a nominee for election as a director, without objection to such nomination).

          “ Covenant Defeasance ” has the meaning set forth in the Indenture except that the covenants included in such definition shall include Articles VI, VII, VIII and IX of this Second Supplemental Indenture and Article Fifteen of the Indenture.

          “ Default ” means any event that is, or after notice or passage of time, or both, would be, an Event of Default.

          “ Domestic Subsidiary ” means a Subsidiary organized under the laws of a jurisdiction located in the United States of America, or any state thereof or the District of Columbia.

          “ DTC ” means The Depository Trust Company, a New York corporation.

          “ Effective Date ” means the closing date of the Acquisition.

          “ Environmental Laws ” means any and all current or future legally-binding statutes, ordinances, orders, rules, regulations, judgments, permits, licenses, authorizations, plans, directives, consent orders or consent decrees of or from any federal, state or local governmental authority, agency or court, or any other binding requirements of governmental authorities relating to (i) the protection of the environment, (ii) any activity, event or occurrence involving hazardous materials, or (iii) occupational safety and health, industrial hygiene, land use or, as relating to the environment, the protection of human, plant or animal health or welfare, in any manner applicable to the Company or any of its Subsidiaries or any of their respective properties or facilities.

          “ ERISA ” means the Employee Retirement Income Security Act of 1974, as amended from time to time.

          “ Euroclear ” means Euroclear Bank, S.A./N.V., as operator of the Euroclear system.

          “ Event of Default ” has the meaning specified in Section 4.1.

          “ Existing Credit Facility ” means that certain Credit Agreement dated as of October 14, 2005 among the Company and the lenders and agents from time to time party thereto, as amended, restated, supplemented, replaced, refinanced or otherwise modified from time to time.

          “ Foreign Subsidiary ” means any Subsidiary other than a Domestic Subsidiary.

          “ GAAP ” means generally accepted accounting principles set forth in the opinions and pronouncements of the Accounting Principles Board of the American Institute of Certified Public Accountants and statements and pronouncements of the Financial Accounting Standards Board or in such other statements by such other entity as may be approved by a significant segment of the accounting profession of the United States, as in effect on the date of this Second Supplemental Indenture.

          “ Group ” means any group of related Persons for purposes of Section 13(d) of the Exchange Act.

          “ Guarantee ” has the meaning specified in Section 9.1.

          “ Guarantor ” means (1) certain of the Company’s Wholly-Owned Subsidiaries, named on the signature pages hereto, (2) upon the closing of the Acquisition, the Target Companies and (3) in the future, certain Subsidiaries that become Guarantors pursuant to Section 6.4, but in each case excluding Persons who cease to be obligated under the Guarantee in accordance with the Second Supplemental Indenture.

          “ Hazardous Materials ” means (i) any chemical, material or substance defined as or included in any environmental law in the definition of “hazardous substances,” “hazardous wastes,” “hazardous materials,” “extremely hazardous waste,” “acutely hazardous waste,” “radioactive waste,” “biohazardous waste,” “pollutant,” “toxic pollutant,” “contaminant,” “restricted hazardous waste,” “infectious waste,” “toxic substances,” or any other term or expression intended to define, list or classify substances by reason of properties harmful to health, safety or the indoor or outdoor environment (including harmful properties such as ignitability, corrosivity, reactivity, carcinogenicity, toxicity, reproductive toxicity, “TCLP toxicity” or “EP toxicity” or words of similar import under any applicable Environmental Laws); (ii) any oil, petroleum, petroleum fraction or petroleum derived substance; (iii) any drilling fluids, produced waters and other wastes associated with the exploration, development or production of crude oil, natural gas or geothermal resources; (iv) any flammable substances or explosives; (v) any radioactive materials; (vi) any friable asbestos-containing materials; (vii) urea formaldehyde foam insulation; (viii) electrical equipment which contains any oil or dielectric fluid containing polychlorinated biphenyls; (ix) pesticide; and (x) any other chemical, material or substance, exposure to which is prohibited, limited or regulated by any governmental authority pursuant to Environmental Laws.

          “ Indebtedness ” means, with respect to any Person, at a particular time, all items of such Person which constitute, without duplication, (a) indebtedness for borrowed money (including capital leases) or the deferred purchase price of Property (other than accounts payable, deferred compensation, customer advances, earn-outs, agreements providing for the holdback of up to 10% of the purchase price relating to an acquisition and accrued expenses incurred in the ordinary course of business), (b) indebtedness evidenced by notes, bonds, debentures or similar instruments, (c) obligations with respect to any conditional sale or other title retention agreement (excluding operating leases), (d) indebtedness arising under acceptance facilities and the amount available to be drawn under all letters of credit issued for the account of such Person and, without duplication,

all drafts drawn thereunder to the extent such Person shall not have reimbursed the issuer in respect of the issuer’s payment of such drafts, (e) all liabilities secured by any Lien (other than carriers’, warehousemen’s, mechanics’, repairmen’s or other like non-consensual Liens arising in the ordinary course of business) on any Property owned by such Person even though such Person shall not have assumed or otherwise become liable for the payment thereof; provided that in the event such Person shall not have assumed or otherwise become liable for the payment thereof, the amount of such liabilities shall be deemed to be the lesser of (i) the fair market value of the assets of such Person subject to such Lien and (ii) the amount of the liability secured by such Lien, (f) that portion of any obligation of such Person, as lessee, which in accordance with GAAP is required to be capitalized on the balance sheet of such Person, (g) Securitized Indebtedness, and (h) all guarantees by such Person of any of the foregoing; provided , however , that, notwithstanding anything to the contrary contained herein, for purposes of this definition, “Indebtedness” shall not include any intercompany indebtedness between or among the Company and any of its Subsidiaries.

          “ Independent Investment Banker ” means one of the Reference Treasury Dealers appointed by the Trustee after consultation with the Company.

          “ Initial Notes ” means Notes in an aggregate principal amount of up to $1,000,000,000 initially issued under this Second Supplemental Indenture in accordance with Section 1.1(2).

          “ Interest Payment Date ” has the meaning specified in Section 1.2(2).

          “ Investment Grade Rating ” means a rating of Baa3 (or better) by Moody’s (or its equivalent under any successor rating category of Moody’s) and a rating of BBB- (or better) by S&P (or its equivalent under any successor rating category of S&P), respectively, and the equivalent investment grade credit rating from any replacement Rating Agency or Rating Agencies selected by the Company under the circumstances permitting the Company to select a replacement agency and in the manner for selecting a replacement agency, in each case as set forth in the definition of “Rating Agency.”

          “ Liens ” means any lien, mortgage, pledge, assignment, security interest, charge or encumbrance of any kind (including any conditional sale or other title retention agreement, any lease in the nature thereof, and any agreement to give any security interest) and any option, trust or other preferential arrangement having the practical effect of any of the foregoing.

          “ Margin Stock ” means any “margin stock”, as said term is defined in Regulation U of the Board of Governors of the Federal Reserve System of the United States of America (or any successor), as the same may be amended or supplemented from time to time.

          “ Maturity Date ” means June 15, 2014.

          “ Moody’s ” shall mean Moody’s Investors Service, Inc., a subsidiary of Moody’s Corporation, and its successors.

          “ NextRx, Inc. ” means NextRx, Inc., a Delaware corporation.

          “ NextRx LLC ” means NextRx, LLC, an Ohio limited liability company.

          “ NextRx Services, Inc. ” means NextRx Services, Inc., a New York corporation.

          “ NextRx Sub ” means each of NextRx Sub I, NextRx Sub II and NextRx Sub III

          “ NextRx Sub I ” means NextRx Sub I, LLC, a Delaware limited liability company.

          “ NextRx Sub II ” means NextRx Sub II, LLC, a Delaware limited liability company.

          “ NextRx Sub III ” means NextRx Sub III, LLC, a Delaware limited liability company.

          “ Note Interest Rate ” has the meaning specified in Section 1.2(1).

          “ Notes ” has the meaning specified in Section 1.1(4).

          “ Notice of Default ” means a written notice of the kind specified in Section 4.1(4).

          “ Obligations ” has the meaning specified in Section 9.1.

          “ Permitted Sale Lease-Back Transactions ” means sales or transfers by the Company or any Subsidiary of any real property, improvements, fixtures, machinery and/or equipment with the intention of taking back a lease thereof; provided , however , that “Permitted Sale-Leaseback Transactions” shall not include such transactions involving machinery and/or equipment (excluding any lease for a temporary period of not more than thirty-six months with the intent that the use of the subject machinery and/or equipment will be discontinued at or before the expiration of such period) relating to facilities (a) in full operation for more than 180 days as of the date hereof and (b) that are material to the business of the Company and its Subsidiaries taken as a whole, to the extent that the sum of the aggregate sale price of such machinery and/or equipment from time to time involved in such transactions (giving effect to payment in full under any such transaction and excluding the Applied Amounts plus the amount of obligations and Indebtedness from time to time secured by Liens permitted under Section 6.1(21) herein, exceeds 15% of the Company’s Consolidated Net Worth.

          “ Person ” includes any individual, corporation, partnership, limited partnership, general partnership, limited liability company, limited liability partnership, business trust, association, joint stock company, joint venture, trust, trust company, bank, association, land trusts, business trusts or other organizations, whether or not legal

entities, incorporated or unincorporated organization or government or any agency or political subdivision thereof.

          “ Property ” means, with respect to any Person, all types of real, personal or mixed property and all types of tangible or intangible property owned or leased by such Person.

          “ Purchase Notice ” means a notice delivered by a Holder in accordance with Section 6.3 in the form set forth in Section 3.3.

          “ Rating Agency ” or “ Rating Agencies ” means each of Moody’s and S&P; provided that if any of Moody’s or S&P ceases to provide rating services to issuers or investors, the Company may appoint another “nationally recognized statistical rating organization” within the meaning of Rule 15c3-1(c)(2)(vi)(F) under the Exchange Act as a replacement for such Rating Agency that is reasonably acceptable to the Trustee.

          “ Redemption Date ,” when used with respect to any Note to be redeemed, means the date fixed for such redemption by or pursuant to this Second Supplemental Indenture.

          “ Redemption Price ,” when used with respect to any Note to be redeemed, means the price at which it is to be redeemed pursuant to this Second Supplemental Indenture.

          “ Reference Treasury Dealer ” means each of Citigroup Global Markets Inc., Credit Suisse Securities (USA) LLC, and J. P. Morgan Securities Inc. (in each case, or their Affiliates and their respective successors); provided that if any of the aforementioned Reference Treasury Dealers resigns, then the respective successor will be a primary United States government securities dealer in The City of New York selected by the Company.

          “ Reference Treasury Dealer Quotations ” means with respect to each Reference Treasury Dealer and any Redemption Date, the average, as determined by the Trustee, of the bid and asked prices for the Comparable Treasury Issue, expressed in each case as a percentage of its principal amount, quoted in writing to the Trustee by such Reference Treasury Dealer at approximately 3:30 p.m. New York City time, on the third Business Day preceding such Redemption Date.

          “ Registrar ” means the Security Registrar for the Notes, which shall initially be Union Bank, N.A., or any successor entity thereof, subject to replacement as set forth in the Indenture.

          “ Regular Record Date ” for interest payable in respect of any Note on any Interest Payment Date means the day that is 15 days prior to the relevant Interest Payment Date (whether or not a Business Day).

          “ Restricted Subsidiary ” means any Subsidiary of the Company that is not an Unrestricted Subsidiary.

          “ S&P ” means Standard & Poor’s Rating Services, a division of The McGraw-Hill Companies, Inc., and its successors.

          “ Securitized Indebtedness ” means, with respect to any Person as of any date, the reasonably expected liability of such Person for the repayment of, or otherwise relating to, all accounts receivable, general intangibles, chattel paper or other financial assets and related rights and assets sold or otherwise transferred by such Person, or any Subsidiary or Affiliate thereof, on or prior to such date.

          “ Significant Subsidiary ” means a Restricted Subsidiary that qualifies as a “significant subsidiary” under Rule 405 of the Securities Act.

          “ Special Mandatory Redemption Date ” means the earlier to occur of (1) January 25, 2010 if the Acquisition has not been completed on or prior to January 9, 2010 or (2) the 30th day (or if such day is not a Business Day, the first Business Day thereafter) following the termination of the Acquisition Agreement for any reason.

          “ Special Mandatory Redemption Notice ” has the meaning specified in Section 5.4(1).

          “ Special Mandatory Redemption Price ” has the meaning specified in Section 5.3.

          “ Stated Maturity ” when used with respect to the Notes or any installment of principal thereof or interest, if any, thereon, means the date specified in such Note as the fixed date on which the principal of the Note or such installment of principal or interest, if any, is due and payable.

          “ Target Companies ” means each of NextRx LLC, NextRx and NextRx Services.

          “ Treasury Rate ” means, with respect to any Redemption Date, the rate per year equal to the semi-annual equivalent yield to maturity or interpolated (on a day count basis) of the Comparable Treasury Issue, assuming a price for the Comparable Treasury Issue (expressed as a percentage of its principal amount) equal to the Comparable Treasury Price for such Redemption Date.

          “ Unrestricted Subsidiary ” means any Subsidiary of the Company that from time to time is not a Guarantor or required to be a Guarantor.

          “ Voting Stock ” means, with respect to any Person as of any date, the Capital Stock of such Person that is at the time entitled to vote generally in the election of the board of directors of such Person.

          “ Wholly-Owned Subsidiary ” when used with respect to any Person means (i) any corporation, association or other business entity of which 100% of the shares of Capital Stock or other equity interests is at the time owned or controlled, directly or indirectly, by such Person or one or more of the other Subsidiaries of such Person (or

combination thereof) and (ii) any partnership, limited liability company or similar pass-through entity the sole partners, members or persons, however designated in corresponding roles, of which are such Person or one or more Subsidiaries of such Person (or any combination thereof).

ARTICLE III

Security Forms

          SECTION 3.1. Form Generally.

          (1) The Notes shall be in substantially the form set forth in Section 3.2 of this Article III, with such appropriate insertions, omissions, substitutions and other variations as are required or permitted by this Second Supplemental Indenture and the Indenture, and may have such letters, numbers or other marks of identification and such legends or endorsements placed thereon as may be required to comply with the rules or regulations of any securities exchange or automated quotation system on which the Notes may be listed or designated for issuance, the Code, or any applicable securities laws, or as may, consistent herewith, be determined by the officers executing such Notes (execution thereof to be conclusive evidence of such approval). All Notes shall be in fully registered form.

          (2) Purchase Notices shall be in substantially the form set forth in Section 3.3.

          (3) Guarantees shall be in substantially the form set forth in Section 3.4.

          (4) The Notes shall be printed, lithographed, typewritten or engraved or produced by any combination of these methods or may be produced in any other manner permitted by the rules of any automated quotation system or securities exchange (including on steel engraved borders if so required by any securities exchange upon which the Notes may be listed) on which the Notes may be quoted or listed, as the case may be, all as determined by the officers executing such Notes, as evidenced by their execution thereof.

          (5) Upon their original issuance, the Notes shall be issued in the form of one or more Global Securities in definitive, fully registered form without interest coupons. Each such Global Security shall be duly executed by the Company, authenticated and delivered by the Trustee and shall be registered in the name of DTC, as Depositary, or its nominee, and deposited with the Trustee, as custodian for DTC. Beneficial interests in the Global Securities will be shown on, and transfers will only be made through, the records maintained by DTC and its participants, including Clearstream and the Euroclear System.

          SECTION 3.2. Form of Note.

[FORM OF FACE OF NOTE]

          [THE FOLLOWING LEGEND SHALL APPEAR ON THE FACE OF EACH GLOBAL SECURITY:

          THIS NOTE IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE THEREOF. THIS NOTE MAY NOT BE EXCHANGED IN WHOLE OR IN PART FOR A NOTE REGISTERED, AND NO TRANSFER OF THIS NOTE IN WHOLE OR IN PART MAY BE REGISTERED, IN THE NAME OF ANY PERSON OTHER THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE.].

          [THE FOLLOWING LEGEND SHALL APPEAR ON THE FACE OF EACH GLOBAL SECURITY FOR WHICH DTC IS TO BE THE DEPOSITARY:

          UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF THE DEPOSITORY TRUST COMPANY, A NEW YORK CORPORATION (“ DTC ”), NEW YORK, NEW YORK, TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF CEDE & CO. OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC (AND ANY PAYMENT IS MADE TO CEDE & CO. OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF DTC), ANY TRANSFER, PLEDGE OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, CEDE & CO., HAS AN INTEREST HEREIN.]

EXPRESS SCRIPTS, INC.

6.250% SENIOR NOTE DUE 2014

          Express Scripts, Inc., a corporation duly organized and existing under the laws of the State of Delaware (herein called the “ Company ”, which term includes any successor Person under the Second Supplemental Indenture referred to on the reverse hereof), for value received, hereby promises to pay to Cede & Co., or registered assigns, the principal sum of                      United States Dollars (U.S.$                      ) on June 15, 2014 and to pay interest thereon, from June 9, 2009, or from the most recent Interest Payment Date to which interest has been paid or duly provided for to but excluding the next Interest Payment Date, which shall be June 15 and December 15 of each year, commencing December 15, 2009, at the per annum rate of 6.250%, or as such rate may be adjusted pursuant to the terms hereof, per annum (the “ Note Interest Rate ”), until the principal hereof is paid or made available for payment.

          The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in the Second Supplemental Indenture, be paid to the Person in whose name this Note is registered at the close of business on the Regular Record Date for such interest, which shall be the day that is 15 days prior to the relevant Interest Payment Date (whether or not a Business Day). Except as otherwise provided in the Second Supplemental Indenture, any such interest not so punctually paid or duly provided for will forthwith cease to be payable to the Holder on such Regular Record Date and may either be paid to the Person in whose name this Note is registered at the close of business on a Special Record Date for the payment of such Defaulted Interest to be fixed by the Trustee, notice of which shall be given to Holders of Notes not less than 10 days prior to the Special Record Date, or be paid at any time in any other lawful manner not inconsistent with the requirements of any automated quotation system or securities exchange on which the Notes may be quoted or listed, and upon such notice as may be required by such exchange, all as more fully provided in the Second Supplemental Indenture. Interest will be computed on the basis of a 360-day year comprised of twelve 30-day months.

          Payment of principal of (and premium, if any) and interest on this Note will be made at the corporate trust office of the Trustee at 551 Madison Avenue, 11th Floor, New York, NY 10022, in such coin or currency of the United States of America as at the time of payment shall be legal tender for the payment of public and private debts. With respect to Global Securities, the Company will make such payments by wire transfer of immediately available funds to DTC, or its nominee, as registered owner of the Global Securities. With respect to certificated Notes, the Company will make such payments by wire transfer of immediately available funds to a United States Dollar account maintained in St Louis, Missouri or New York, New York to each Holder of an aggregate principal amount of Notes in excess of U.S. $5,000,000 that has furnished wire instructions in writing to the Trustee no later than 15 days prior to the relevant payment date. If a Holder of a certificated Note (i) does not furnish such wire instructions as provided in the preceding sentence or (ii) holds $5,000,000 or less aggregate principal amount of Notes, the Company will make such payments by mailing a check to such Holder’s registered address.

          Reference is hereby made to the further provisions of this Note set forth on the reverse hereof, which further provisions shall for all purposes have the same effect as if set forth at this place.

          Unless the certificate of authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Note shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose.

          IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed.

CERTIFICATE OF AUTHENTICATION

This is one of the Securities of the series designated referred to in the within-mentioned Indenture.

Dated:

UNION BANK, N.A.,
as Trustee

[FORM OF REVERSE OF NOTE]

          1. Indenture . This Note is one of a duly authorized issue of securities of the Company designated as its “6.250% Senior Notes due 2014” (herein called the “ Notes ”), issued under a Second Supplemental Indenture, dated as of June 9, 2009, to an indenture, dated as of June 9, 2009 (as it may be amended or supplemented from time to time in accordance with the terms thereof, the “ Indenture ” and herein with the Second Supplemental Indenture, collectively, the “ Indenture ”), between the Company, the Guarantors and Union Bank, N.A., as Trustee (herein called the “ Trustee ,” which term includes any successor trustee under the Indenture), to which reference is hereby made for a statement of the respective rights, limitations of rights, duties and immunities thereunder of the Company, the Guarantors, the Trustee and the Holders of the Notes and of the terms upon which the Notes are, and are to be, authenticated and delivered. The aggregate principal amount of Initial Notes Outstanding at any time may not exceed $1,000,000,000 in aggregate principal amount, except for, or in lieu of, other Notes of the Series pursuant to Sections 304, 305, 306, 906 or 1107 of the Indenture and except for any Notes which, pursuant to Section 303 of the Indenture, are deemed never to have been authenticated and delivered. The Second Supplemental Indenture pursuant to which this Note is issued provides that Additional Notes may be issued thereunder, if certain conditions are met.

          All terms used in this Note which are defined in the Indenture shall have the meanings assigned to them in the Indenture. In the event of a conflict or inconsistency between this Note and the Indenture, the provisions of the Indenture shall govern.

          2. Optional Redemption . At any time prior to Maturity, the Company may at its option redeem all or a part of the Notes upon not more than 60 nor less than 30 days prior notice, at a redemption price equal to the greater of: (i) 100% of the aggregate principal amount of any Notes being redeemed, plus accrued and unpaid interest on the Notes to the Redemption Date; or (ii) the sum of the present values of the remaining scheduled payments of principal of and interest on the Notes to be redeemed (exclusive of unpaid interest accrued thereon to the Redemption Date) discounted to the Redemption Date on a semi-annual basis (assuming a 360-day year comprised of twelve 30-day months) at the Treasury Rate plus 50 basis points, plus, unpaid interest on the Notes to be redeemed, accrued to the Redemption Date.

          3. Mandatory Redemption . Except as provided in Sections 4 and 5 below, the Company is not required to make mandatory redemption or sinking fund payments with respect to the Notes.

          4. Special Mandatory Redemption . If for any reason (i) the Acquisition is not consummated on or prior to January 9, 2010 or (ii) the Acquisition Agreement is terminated at any time prior thereto, then the Company will redeem all the Notes on the Special Mandatory Redemption Date at a redemption price equal to 101% of the aggregate principal amount of the Notes plus accrued and unpaid interest from the date of initial issuance to but excluding the Special Mandatory Redemption Date (subject to the right of Holders on the relevant Regular Record Date to receive interest due on the relevant Interest Payment Date).

          5. Change of Control Triggering Event . In the event of a Change of Control Triggering Event, the Holders may require the Company to purchase for cash all or a portion of their Notes at a purchase price equal to 101% of the aggregate principal amount of the Notes, plus accrued and unpaid interest, if any, pursuant to the provisions of Section 6.3 of the Second Supplemental Indenture.

          6. Global Security . If this Note is a Global Security, then, in the event of a deposit or withdrawal of an interest in this Note, including an exchange, transfer, redemption, repurchase or conversion of this Note in part only, the Trustee, as custodian of the Depositary, shall make an adjustment on its records to reflect such deposit or withdrawal in accordance with the Applicable Procedures.

          7. Defaults and Remedies . If an Event of Default shall occur and be continuing, the principal of all the Notes, together with any unpaid premium and accrued interest to the date of declaration, may be declared due and payable in the manner and with the effect provided in the Second Supplemental Indenture. Upon payment (i) of the amount of principal so declared due and payable, together with any unpaid premium and accrued interest to the date of declaration, and (ii) of interest on any overdue principal