FIRST AMENDMENT TO RIGHTS AGREEMENT BETWEEN ORCHID BIOSCIENCES, INC. AND AMERICAN STOCK TRANSFER & TRUST COMPANY

This First Amendment to Rights Agreement (the “Amendment”) is made as of this 31^st day of March, 2003 by and between Orchid BioSciences, Inc., a Delaware corporation (the “Company”), and American Stock Transfer & Trust Company as rights agent (the “Rights Agent”). Capitalized terms used but not defined herein shall have the meanings given to such terms in the Purchase Agreement (as defined below).

WHEREAS, the Company has entered into a Securities Purchase Agreement dated as of March 31, 2003 by and among the Company and the Purchasers set forth on the execution pages thereof (the “Purchase Agreement”), pursuant to which the Company will issue and sell to the Purchasers units, each consisting of (i) one share of the Company’s Series A Convertible Preferred Stock, par value $.001 per share (the “Preferred Shares”), convertible into 22,222.22 shares of the Company’s common stock, par value $.001 per share (the “Common Stock”), and (ii) a warrant (the “Warrants”) to acquire 6,666.67 shares of Common Stock;

WHEREAS, the Company and the Rights Agent are parties to a Rights Agreement dated as of July 27, 2001 (the “Rights Agreement”); and

WHEREAS, the parties desire to amend the Rights Agreement in connection with the execution and delivery of the Purchase Agreement, the issuance and sale of the Preferred Shares and Warrants and the issuance of Common Stock upon the conversion of the Preferred Shares and the exercise of the Warrants, and the Company and the Rights Agent have executed and delivered this Amendment.

NOW, THEREFORE, in consideration of the foregoing and the mutual agreements herein set forth, the parties hereby agree as follows:

1.     The definition of “Acquiring Person” set forth in Section 1(a) of the Rights Agreement is hereby amended by adding the following sentence to the end of such definition:

“Notwithstanding the foregoing, none of SDS Capital Partners, SDS Merchant Fund, LP, BayStar Capital II, L.P., DMG Legacy Fund LLC, DMG Legacy Institutional Fund LLC or DMG Legacy International Ltd., or any affiliate thereof (each a “Preferred Purchaser” and collectively, the “Preferred Purchasers”) shall be or become an Acquiring Person by reason of (i) the execution or delivery of the Securities Purchase Agreement dated as of March 31, 2003 by and among the Company and the Purchasers set forth on the execution pages thereof (the “Purchase Agreement”), (ii) the purchase of shares of Series A Convertible Preferred Stock, par value $.001 per share, of the Company (the “Preferred Shares”) pursuant to the terms and conditions of the Purchase Agreement, (iii) the purchase of warrants to purchase shares of Common Stock of the Company (the “Warrants”) pursuant to the terms and conditions of the Purchase Agreement, (iv) the issuance of shares of Common Stock of the Company upon the conversion of Preferred Shares purchased pursuant to the terms and conditions of the Purchase Agreement, (v) the issuance of shares of Common Stock of the Company as a dividend on the Preferred Shares purchased pursuant to the terms and conditions of the Purchase Agreement or (vi) the issuance of shares of Common Stock of the Company upon the exercise of Warrants purchased pursuant to the terms and conditions of the Purchase Agreement.”