Synovial fluid studies have been made on 43 patients with rheumatic disease. Lymphocytes separated by a 2-stage procedure were examined for the presence of activated large lymphoid cells or immunoblasts. Such immunoblasts were found in 19 of 21 patients with classical rheumatoid arthritis and 7 of 10 patients with seronegative polyarthritis, including patients with Still's disease, psoriatic arthritis, and ankylosing spondylitis. No immunoblasts were seen in synovial fluid from osteoarthrosis or in the inflammatory but nonimmune synovial fluid from crystal-induced arthritis. The presence of immunoblasts showed a correlation with the lymphocyte count in the synovial fluid but not with the total white cell count. Preliminary studies confirm the spontaneous metabolic activity of these cells by autoradiography and show them by scanning electron microscopy to have a villous surface membrane. Simultaneous peripheral blood studies showed a lower incidence of immunoblasts than in the synovial fluid. It is suggested that these cells originate in the synovial membrane. In view of the known migration characteristic of immunoblasts these cells may be important in the spread of immune arthritis as well as being markers of disease activity.