The immune response of T cells to self-HLA antigens on autologous non-T cells is known as the autologous mixed lymphocyte reaction (AMLR), and is defective in various diseases. We have investigated the effects of exogenous IL-10, a potential agent to treat various inflammatory diseases, on cytokine production induced by two-way AMLR in human peripheral blood mononuclear cells (PBMC). Effects of exogenous IL-4 were also investigated. IL-10 suppressed IL-6, IL-8, TNF-alpha and GM-CSF production when added at the beginning of culture and added 24 h after incubation. It abolished IL-1 alpha production only when added at the beginning of culture. IL-10 did not inhibit IL-3 production. The pattern of suppression by IL-10 of cytokine production induced by anti-CD3 mAb or PHA was similar to that induced by AMLR. Although IL-4 showed a largely similar pattern of inhibition when added at the beginning of culture, the level of inhibition was much lower than that of IL-10. IL-4 did not inhibit cytokine production when added 24 h after culture. These results indicate that IL-10, but not IL-4, is a potent inhibitor to cytokine production induced by two-way AMLR.