Membrane and transformation characteristics of lymphocytes isolated from the synovial membrane and from paired peripheral blood samples, obtained from patients with classical rheumatoid arthritis, were studied. Synovial tissue lymphocytes were isolated by a new technique. Two suspensions of peripheral blood lymphocytes were studied: one isolated by Ficoll-Isopaque density gradient centrifugation, the other enriched in T cells by an additional step of 1 hour nylon wool column filtration. All suspensions were characterised by the percentages of mononuclear phagocytic cells, and T and B lymphocytes. The spontaneous 3H-thymidine uptake of synovial tissue lymphocyte suspensions always exceeded that of the peripheral blood lymphocyte suspensions. The in-vitro responsiveness of synovial tissue lymphocytes to PHA, Con-A, and PWM, as measured by 3H-thymidine uptake, was always consistently lower than that of paired peripheral blood lymphocytes whether or not enriched in T cells. The responsiveness to antigens, including PPD, varidase, and an antigen cocktail consisting of varidase, trychophyton, and Staphylococcus aureus antigen, showed the same effect. No dissociation was found between the response to PPD and the other antigens studied. These results suggest that the relative unresponsiveness to mitogens and antigens of synovial tissue lymphocytes in comparison with blood lymphocytes is not caused by mononuclear phagocyte contamination, but either by different subsets of T lymphocytes or by different functional states of T lymphocytes present in the synovial membrane and peripheral blood of patients with rheumatoid arthritis.