Interactions of the vascular endothelium and cells of the immune system play a major role in the initiation and sustaining of cell mediated immune response in autoimmune diseases, chronic inflammatory processes and graft rejection. In the present investigation, the initial step of T cell-endothelial cell interactions, namely the adhesion of T cells to endothelial cells, was studied with special emphasis on the binding of T cells activated in vitro with lectins and by allogeneic cells as well as on the effect of pretreating endothelial cells with IFN-gamma. Human endothelial cells (EC) were isolated from the umbilical cord vein; human foreskin fibroblasts (HFF) served as control cells. While resting T cells demonstrated an adherence of 53% to EC and 20% to HFF, PHA blasts showed a binding of 90% to EC and 59% to HFF. Similar results were obtained using MLC blasts from mixed leukocyte cultures. Thus, the activation process triggered a striking enhancement of T cell binding not only to EC, but also to HFF that were taken as mesenchymal control cells. Pretreatment of EC and HFF with IFN-gamma, inducing Ia antigens on both cell populations, led to a significant increase of binding of resting T cells to EC. Of special interest, T lymphocytes also exhibited a considerably increased adherence to Ia-positive rheumatoid synovial fibroblasts. Taken together, these findings indicate that both the activation of T cells as well as endothelial cells results in a greatly enhanced binding.