The effects of concanavalin A (Con A) on murine plaque-forming cell (PFC) responses to sheep erythrocytes in vivo are described. Both IgM and IgG PFC responses were profoundly suppressed in mice injected with 50 μg or more of Con A 1-2 days before immunization. Conversely, injection with Con A 1-3 days after immunization enhanced PFC responses. Immune responses were also markedly depressed in mice injected with Con A before irradiation and subsequent reconstitution with normal spleen cells. Suppression of immune responses derived primarily from potent inhibitory influences expressed during the phase of exponential PFC proliferation. Secondary immune responses were comparably suppressed by administration of Con A prior to secondary immunization. In marked contrast to the effects of Con A on antibody synthesis, however, development of immunologic memory was not inhibited by injection of Con A prior to primary immunization. The data therefore suggest that development of antibody responses and the generation of memory cell pools may be independently regulated. © 1975.