Integrin receptors are Important for regulating lymphocyte reclrculatlon and recruitment to sites of inflammation. Transfoctants of the B cell lymphoma 38C13 were generated that differ exclusively in the expression of integrin β1 or β7 subunlts allowing for a functional comparison of lymphocyte Peyer's patch HEV adhesion molecule 1 (LPAM-1) (α4β7) and very late antigen 4 (VLA-4) (α4β1) in an Identical cellular environment. Whereas 38-β7 transfectants bound to purified and cellular mucosal addressin cell adhesion molecule (MAdCAM-1), unstlmulated 38-β1 cells failed to bind MAdCAM-1. Treatment of 38-β1 cells with Mn2+ but not with PMA induced low level binding to MAdCAM-1. MAdCAM-1 adhesion of 38-β7 cells was constitutive and not enhanced by Mn2+ treatment. Similarly, MAdCAM-1-dependent adhesion to mucosal high endothellal venules was shown for 38-β7 but not for 38-β1 cells. The results therefore establish the LPAM-1 - MAdCAM-1 Interaction as the functionally dominant adhesion pathway for regulating lymphocyte homing to mucosal sites. Nonetheless, the activated VLA-4 on some lymphocytes may be involved in MAdCAM-1 recognition or promote binding to MAdCAM-1 In other tissues. By contrast, 38-β7 and 38-β1 transfectants did not differ in their binding capacity for vascular cell adhesion molecule 1 (VCAM-1) or fibronectin and LPAM-1 did not display any preference for interacting with either MAdCAM-1 or VCAM-1. LPAM-1 may therefore contribute significantly to cellular functions previously attributed to VLA-4. Interestingly, functional analysis of the intraepithellal lymphocyte integrin αIELβ7 which Is structurally related to LPAM-1 did not reveal detectable binding activity for MAdCAM-1, VCAM-1, or fibronectin.