The present study investigated the intrinsic blastogenic reactivity within T and non-T lymphocyte populations as well as between these populations in the autologous and allogeneic mixed lymphocyte reactions (MLR). T cell-depleted lymphocytes exhibited after 6 days in culture, high levels of intrinsic blastogenic activity that were sensitive to irradiation and in vitro hydrocortisone. Depletion of adherent cells shifted the peak T cell-depleted intrinsic blastogenesis from 6 days in culture to 2 to 3 days after initiation of culture. T cellenriched cells displayed low intrinsic blastogenic responses that were relatively unaffected by irradiation and in vitro hydrocortisone. The removal of adherent cells from T cell-depleted suspensions (stimulators) augmented both the autologous and allogeneic MLR, whereas irradiation of cells had no effect on these reactions. In vitro hydrocortisone suppressed the autologous MLR and, to a much lesser extent, the allogeneic MLR. I.V. administration of hydrocortisone to normal volunteers suppressed the autologous MLR at 4 hr after injection. The responsiveness of T cells obtained at 4 hr to autologous and allogeneic non-T cell stimulation was markedly diminished. Non-T cells obtained 4 hr after i.v. hydrocortisone had greater stimulatory capacity for both the autologous and allogeneic MLR than did T cell-depleted cells obtained before hydrocortisone administration. These studies demonstrate that autologous and allogeneic intercellular interactions between lymphoid cells are susceptible to a variety of in vitro and in vivo influences and that such interactions may reflect relevant immunoregulatory events occurring in vivo.