A B S T R A C T An average of 5-9% of human peripheral blood of T lymphocytes form rosettes with autologous erythrocytes (ARFT). This population responded only slightly against autologous and allogeneic non-T cells. In contrast, T cells that did not form rosettes with autologous erythrocytes (NRFT) proliferated to a greater degree in auto-and allogeneic mixed lymphocyte reactions (MLR) and also in reactions to trinitrophenyl (TNP) modified autologous non-T cells (TNP-auto-MLR) as compared with ARFT or unfractionated T cells. The ARFT populations could suppress the increased allogeneic (allo)MLR and TNPauto-MLR of NRFT when the ARFT were added to the NRFT at the beginning of the cultures.Fluorescence-activated cell-sorter (FACS) analysis of these freshly obtained T cell fractions using monoclonal antibodies to subpopulations of T cells did not demonstrate any selective gain or loss of T cell subsets in the ARFT and NRFT as compared with unfractionated T cells. But when each T cell fraction was cultured separately for a week in the presence of autologous non-T cells (auto-MLR) and the cells were again analyzed' by fluorescence-activated cell sorter, there was an increase in OKT8-positive cells (suppressor/cytotoxic subset) only in the ARFT fraction. The above findings strongly suggest that suppressor T cells are generated from the ARFT fraction during an auto-MLR, these may then regulate the responses of NRFT.