Active immunization of mice with whole cell vaccine or cell surface polysaccharide from either the Smith diffuse strain ofStaphylococcus aureusor SS-615 (type Iaof group B streptococci) protected against challenge by either the homologous or heterologous strains. In the peritoneal cavity of mice immunized with either of these organisms rapid phagocytosis and reduction of the viable cells was observed at 6 h after the challenge. Cell surface polysaccharides extracted from strains Smith diffuse and SS-615, both prepared by the same procedure as that of the Smith surface antigen, were capable of absorbing the protective antibody in rabbit hyperimmune sera prepared with homologous or heterologous strains.