Activation of resting T cells to proliferate is usually accompanied by their expression of interleukin 2 receptors (IL-2R) and secretion of (IL-2). We studied the mechanisms by which human blood-derived dendritic cells (DC) and monocytes induce IL-2R and stimulate IL-2 secretion in autologous and allogeneic mixed luecocyte reaction (auto- and allo-MLR, respectively). We found that only DC were fully effective as stimulator cells in MLR. DC stimulated both autologous and allogeneic T cells to express high-affinity IL-2R, secrete IL-2, and vigorously proliferate in MLR. The stimulatory properties of monocytes were more complicated: although they stimulated the proliferation in allogeneic MLR, the proliferation rates, duration, and amount of IL-2 secretion were different than in DC-induced MLR. Autologous T cells did not proliferate in response to monocytes, but were induced to express the low-affinity IL-2R. If the cultures were supplemented with exogenous recombinant IL-2, the proliferative responses to DC and monocytes in auto- and allo-MLR were of the same magnitude, indicating that the responsiveness to IL-2 was stimulated by both the stimulator cells. The stimulator cell number was important, since large numbers of monocytes, but not of DC, were suppressive to the proliferative responses. Thus, we concluded that the higher capacity of DC, as compared to monocytes, to stimulate T-cell proliferation is based primarily on the more efficient stimulation of IL-2 secretion.