Human peripheral blood monocytes (M phi) were separated into Fc receptor positive (FcR+) and FcR- subsets by rosetting with O,Rh+ human erythrocytes coated with IgG anti-D antibody, followed by density gradient centrifugation and adherence. The FcR+M phi suppressed PHA- and PPD-induced lympho-proliferation and also exhibited a strong cytostatic effect against tumor cell lines in vitro, but were a poor source of antigen-presenting cells. In contrast, the FcR- subset did not cause suppression but was highly active in the presentation of PPD to T cells and in stimulation of both allogeneic mixed lymphocyte reaction (allo-MLR) and autologous (auto-MLR). PWM-induced immunoglobulin secretion in vitro was greatly enhanced by the FcR- but not the FcR+ subset. Nevertheless, both FcR+ and FcR- subsets showed comparable HLA-DR antigen expression. These results indicate that human M phi, like lymphocytes, may consist of several subsets that differ significantly in their immunologic functions.