In an attempt to determine the possible role of peritoneal phagocytes in the initiation of agglutinin response to RBC, bio-assay curves were first constructed to assess the immunogenicity of the test antigen by culturing in vivo varying numbers of sheep RBC with 107 primed mouse spleen cells. This number of spleen cells, when optimally stimulated, synthesized as much antibody as an intact mouse. Observations made at varying time intervals after culture of RBC with fixed or varying numbers of phagocytes revealed that immunogens or immunogen-like substances were neither released nor stored by phagocytes actively engaged in phagocytosis in either in vitro or in vivo conditions. Furthermore, when fixed or varying numbers of peritoneal phagocytes were cultured in vivo together with a fixed number of spleen cells and RBC, they were shown to be destructive competitors rather than “symbionts” of spleen cells undergoing either a primary or secondary antibody response. Finally, non-opsonized and opsonized RBC were injected into glycogen-treated and untreated mice by the intraperitoneal and intravenous routes, and the results showed that minimum response was obtained when opsonized RBC were injected i.p. into glycogen-treated mice, and maximum response when nonopsonized RBC were injected i.v. into untreated mice. These results show that peritoneal phagocytes respond to foreign RBC as scavenger cells and are not essential for the initiation of antibody response.