The human autologous mixed lymphocyte reaction represents the proliferative response of T cells to determinants presented on autologous non-T cells. Purified T4+ cells vigorously proliferate in response to stimulation by either (B + null) cells or M phi, whereas purified T8+ cells proliferate very little without a source of help. Such help can be provided by mitomycin C-treated T4+ cells, which indicates that proliferation of T4+ cells is not necessary for the help. M phi suppress the human AMLR, as measured by the response of T cells to stimulation by (B + null) cells. The target of this M phi-induced suppression was found to be the T4+ inducer cell. In contrast to the suppressive effects of M phi on T4+ cells, M phi did not suppress T8+ cells. The available data suggest that the human AMLR is a two-part inducer circuit. One part can be stimulated preferentially by M phi and the other by (B + null) cells; however, M phi prevent activation of the (B + null) cell part of the circuit. These results may provide an explanation for the differential activities of different regulatory circuits without and also with antigenic stimulation.