N-(3, 5-Dichlorophenylsulfonyl)-(R)-thioprolyl biarylalanine 10a has been identified as a potent and specific antagonist of the α4β1 integrin. Altering the configuration of thioproline from R to S led to a series of dual antagonists of α4β1 and α4β7, and the N-acetyl analogue 8b was found to be the most potent dual antagonist. A binding site model for α4β1 and α4β7 is proposed to explain the structure–activity relationship.