Heterogeneous subpopulations of peripheral blood (PB) mononuclear cells that are capable of being activated by concanavalin A (Con A) to suppress the pokeweed mitogen (PWM)-induced anti-sheep red blood cell (SRBC) direct plaque-forming cell (PFC) response of human B cells have been described. Removal of adherent cells by passage over a Sephadex G-10 column or by plating of PB mononuclear cells on plastic surfaces did not affect the generation of Con A-activated suppressor cells (SC) (p < 0.01). Separation of PB cells into T cell-enriched (TCE) and T cell-depleted (TCD) suspensions by SRBC rosetting procedures demonstrated maximal Con A-activated suppression in each of these subpopulations (p < 0.001). Separation of the TCE fraction into T cells that bear Fc receptors for IgG (T.G) and those that do not (T.G-depleted) demonstrated submaximal suppression in each group alone. The T.G-depleted subpopulation suppressed to 50 ± 22% of control whereas the T.G fraction obtained by 7S EA rosetting did not suppress (128 ± 66% of control). However, T.G-enriched cells obtained, without activating the 7S Fc receptor, by depleting TCE fractions of T cells bearing an Fc receptor for IgM (T.M-depleted) did suppress maximally. Finally, separation of unfractionated PB mononuclear cells into those cells that possess complement (C) receptors (CR positive) and those that do not (CR negative), demonstrated that there was significant Con A-activated suppression in the CR-negative fraction of cells (p < 0.01) whereas the Con A-activated CR-positive cell did not suppress (p > 0.2). Thus, these studies demonstrate that cells that are capable of being activated by Con A to suppress the PWM-induced PFC response of normal human PB mononuclear cells are found in both the TCE and TCD fractions. In the TEC suspensions, Con A SC are found in both IgG Fc receptor positive and negative fractions, although IgG Fc receptor negative cells were less potent suppressors than IgG Fc receptor positive cells. In the TCD suspension, Con A SC are nonadherent, E-rosette-negative, Cr-negative cells.