The effects of bucillamine on the proliferation of human peripheral blood mononuclear cells and their production of interferon-gamma (IFN-gamma) and interleukin 2 (IL-2) were investigated in vitro. Bucillamine, a synthetic SH compound, has recently been developed as a disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA), and its clinical usefulness for RA has been proved. Lymphocyte proliferative response to phytohaemagglutinin was significantly inhibited by bucillamine at concentrations of 1 to 100-mu-M in a concentration-dependent manner. Subsequently, bucillamine inhibited the production of immunoregulatory lymphokines, including IFN-gamma and IL-2, simultaneously. In contrast, D-penicillamine and tiopronin (SH compounds analogous to bucillamine) did not show any apparent effect on the production of these lymphokines at the same concentrations. Apparent immunosuppressive activities are suggested for bucillamine, and it may play a significant role in the suppression of synovitis with RA by inhibiting the overall production of IFN-gamma and IL-2.