T lymphocytes interact with extracellular matrix proteins (ECMPs) through the ?-1 or very late antigen (VLA) integrins. VLA integrins comprise a common ? chain with different a-subunits that influence ECMP-binding specificity. They are costimulatory molecules, involved in adhesion and cellular migration. Reports on the role of the ECMP fibronectin in costimulating T cells have described therapeutic effects of VLA antibodies or peptide ligands in inflammatory/autoimmune disease models or transplantation. In contrast, the ECMP type I collagen has inconsistent effects on T cell activation, with most reports finding that resting peripheral blood (PB) T cells do respond. However, here the authors suggest that resting PB T cells are not representative of populations of extravascular, activated, effector cells that encounter immobilised ECMPs and that are involved in the pathogenesis of inflammatory/autoimmune diseases. To address this they have investigated the costimulatory effects of ECMPs on both freshly isolated human PB CD4+ and CD8+ T cells, and antigen- or mitogen-stimulated CD4+ and CD8+T cell lines used as models of the extravascular effector cells encountered in disease.