The mucosal vascular addressin, MAdCAM-1, is an immunoglobulin superfamily adhesion molecule for lymphocytes that is expressed by mucosal venules and helps direct lymphocyte traffic into Peyer’s patches (PP) and the intestinal lamina propria. We demonstrate that the lymphocyte integrin a487, also implicated in homing to PP, is a receptor for MAdCAY-1. Certain antibodies to a4 and 87 integrin chains but not to the 82 integrin LFA-1 inhibit lymphocyte binding to purified MAdCAM-and to MAdCAM- transfectants. Lymph node lymphocytes, a487+ TKl lymphoma cells, and a 87-transfectedvariant of an a4+ Bcell line, 38C13, bind constitutively to MAdCAM-1. Binding is enhanced by Mn++-induced integrin activation. The related integrin a481 supports efficient binding to VCAM-1 but not to MAdCAM-1, even after integrin activation, indicating that MAdCAM-is a preferential ligand for~ 487. a487 can also bind VCAM-1, but this requires greater integrin activation than binding to MAdCAM-1. The findings imply a setsctive role for the interaction of a487 and MAdCAM-lymphocyte in homing to mucosal sites.