The integrin alpha 4 beta 7 and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) are molecules involved in the normal recirculation of lymphocytes between the blood and the gastrointestinal tract. These molecules may play a complementary and significant role in animal models of colitis. We have investigated the structural interaction between alpha 4 beta 7 and MAdCAM-1. Site-directed mutagenesis studies of the MAdCAM-1 molecule has led to the identification of the amino acid residue (LDT) in the loop between beta strands C and D of the Ig-superfamily-like folds being involved in the adhesive and cell activation functions of MAdCAM-1 with alpha 4 beta 7.