In rabbits, purified streptococcal pyrogenic exotoxin, at 0.002 of the ld(50) dose, suppressed the antibody response to injected sheep erythrocytes. The antibody suppressed was determined by density gradient ultracentrifugal analysis to be of the 19S class. Background serum antibody (50% hemolytic units), as determined photometrically, correlated well with background antibody-forming spleen cells, as determined by the hemolytic-plaque technique. The exotoxin induced neither positive nor negative changes in background antibody levels, but suppressed the early secondary response to injected antigen. A comparison and control experiment showed that purified gram-negative bacterial endotoxin at identical protocol did not induce antibody suppression, but did induce the well-known adjuvant effect. Because streptococcal pyrogenic exotoxin is known to inhibit the phagocytic function of the reticuloendothelial system (RES), these data strongly support the concept that antigen is processed by cells of the RES before it evokes a secondary immune response. The results also demonstrated that streptococcal pyrogenic exotoxin may play a unique role in lowering the acquired defense of the host against infection. If the anamnestic immune response of the host is temporarily suppressed, then the host-parasite balance would be upset in favor of the parasite.