Immunosuppression by antibody was studied in mice passively immunized at birth and challenged with antigen 6 weeks later. At the time of antigen (sheep red blood cells (SRBC)) administration none of the antibody (anti-SRBC) given at birth was detectable by conventional serologic techniques. However, evidence for persistence of antibody was obtained by the demonstration that spleen cells from normal mice, when transferred to irradiated, passively immunized mice, were unable to mount a primary immune response. By contrast, spleen cells from mice primed with SRBC elaborated a normal anamnestic response when transferred to irradiated, passively immunized mice. The locus of action of immunosuppressive antibody was studied in several ways. No evidence was obtained that the effect was due to binding of antibody to unproccessed antigen. SRBC retrieved from passively immunized mice were immunogenic in normal mice. Spleen cells from passively immunized mice responded normally when transferred to irradiated mice, thus excluding lymphoid cells as the site of action of immunosuppressive antibody. However, when macrophages from passively immunized mice were “fed” SRBC, they failed to induce an immune response in normal recipients. It was concluded that, in the system studied, antibody exerts its immunosuppressive effects at the level of the macrophage.