In this study we investigated the receptors by which murine lymphocytes bind to collagen and laminin. To identify the collagen and laminin receptors, we generated three monoclonal antibodies, two of which (HM alpha 1 and HM alpha 2) could inhibit adhesion of activated T cells to collagen and laminin and one of which (HM alpha 6) could inhibit that to laminin. Biochemical studies showed that the antigens recognized by HM alpha 1, HM alpha 2, and HM alpha 6 are the mouse homologues of human VLA-1, VLA-2, and VLA-6, respectively. Finally, we demonstrated that both VLA-1 and VLA-2 contribute to the functional interaction between collagen and activated T cells, since HM alpha 1 and HM alpha 2 specifically inhibited collagen-induced TNF secretion from activated T cells. These results indicate that VLA-1 and VLA-2 play an important role in regulating adhesion and cytokine production of activated T cells.