Human autologous and allogeneic mixed lymphocyte reactions (MLR) were studied using various T cell subsets as responding cells. T cells expressing Fc gamma receptor for IgG (TG) were weak responder while T cells with Fc mu receptor and T cells lacking Fc receptor responded vigorously in both types of MLR. Percoll-separated T cells of low density (TL) enriched for TG cells were, however, excellent responders in autologous MLR, whereas T cells of high density (TH) were the major responders in allogeneic MLR. Continuous presence of or short-term pulse with aggregated IgG significantly reduced the autologous MLR of unfractionated T and TL cells while largely sparing proliferation in allogenic MLR. These findings are discussed with respect to diminished autologous MLR reactivity in certain autoimmune diseases.