The ability of transplanted marrow-thymus cell mixtures to generate antibody-forming cells in irradiated syngeneic or F(1) hybrid mice when immunized with sheep erythrocytes 18 hours later was determined. Much fewer anti-sheep plaque-forming cells (PFC) were detected in spleens of F(1) hybrid mice. Adrenalectomy, use of infant recipient mice, or preimmunization of donors or hosts did not prevent the suppression; the grafting of irradiated donor-type spleen cells (source of "accessory" cells) produced only an additive effect. Parental marrow and thymus cells were able to generate new precursors of PFC and specific inducer cells, respectively, in spleens of F(1) hybrid mice, as detected by two-step experiments utilizing parent-strain secondary recipient mice. The suppression depended upon transferring parental strain thymus cells into F(1) hybrid mice and was seen irrespective of the marrow donor strain. When irradiated mice were immunized twice (on the day of transplantation and 4 days later), there was only marginal suppression of antibody production when marrow cells only or marrow plus thymus cells were transplanted. Thus, it appears that an excess of thymus-derived "suppressor" cells is generated upon exposure to alloantigens and inhibit terminal differentiation of antibody-forming cells in a noncytotoxic manner. Mature PFC themselves were not the targets of suppression. The method of immunization probably determines the relative functional capacity of thymus-derived "helper" and suppressor cells.