Human mononuclear cell supernatants were obtained by incubating 3 X 10(6) cells per ml of Dulbecco's modified Eagles medium at 37 degrees C for 24 h or 48 h, either in presence or absence of phytohaemagglutinin. After removal of intact cells, the supernatants were dialysed and diluted (1:1, 1:2, 1:5, 1:10) again using the above medium. The diluted supernatants, containing a final concentration of 10% (v/v) human platelet-factor poor serum, were found to stimulate the proliferation of human synovial cells in culture and to increase both the total amount of collagen and the percentage of Type III collagen synthesized by these cells. Incubation of the mononuclear cells in presence of phytohaemagglutinin appeared to further enhance the stimulatory effects of the supernatants upon the synovial cells. Since activated mononuclear leucocytes such as lymphocytes and macrophages are present in rheumatoid synovia, this study suggests that factors released from activated mononuclear leucocytes may play an important role in the proliferation of rheumatoid synovial tissue and development of the pannus.