T cells interact with the extracellular matrix via integrin receptors and these interactions affect both cellular localization and proliferation. The importance of these interactions in retrovirus-induced diseases, however, remains less clear. In the present study, we investigated changes in T cell adhesion to extracellular matrix proteins by HTLV-I expressing cell lines and human peripheral blood lymphocytes infected with HTLV-I by cocultivation. Cell lines and acutely infected primary peripheral blood lymphocytes demonstrated enhanced adhesion to fibronectin. Acute infection of peripheral blood lymphocytes increased the expression of alpha 5 beta 1 and alpha 4 beta 1 integrins. Antibodies to the alpha 4, alpha 5, and beta 1 subunits inhibited attachment of infected cells to fibronectin. We conclude that HTLV-I infection is associated with an increase in the expression of both the classical fibronectin receptor and the receptor for the alternatively spliced domain of fibronectin on peripheral blood lymphocytes. HTLV-I-related alterations in cell surface adhesion molecules may contribute to the abnormal proliferation of T cells in adult T cell leukemia (ATL) or to the abnormal localization of activated or infected T cells to the central nervous system of patients with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM).