Cell walls from Streptococcus pyogenes strain Sv (Group A, M type 3) were lysed with M1 endo-N-acetylmuramidase, and the group A-specific carbohydrate antigen was purified by Sephadex G-100 gel filtration. The initial eluting antigen (M1gA) peak was assessed for mitogenic and polyclonal lymphocyte-activating properties in murine spleen cell cultures. Good mitogenic responses were induced over a broad dose range (1–100 μg) with M1gA in both BALB/c and C3H/HeJ splenic cultures. Similar mitogenic responses were induced in nude (nu/nu) and nu/+ splenic cultures, suggesting that M1gA is a B cell mitogen. The M1gA induced anti-trinitrophenyl, anti-sheep erythrocytes, and anti-horse erythrocytes polyclonal plaque-forming cell responses in splenic cell cultures. Studies with purified splenic B cells and M1gA suggest that the mitogenic responses were indeed thymic independent. These studies clearly indicate that native group A carbohydrate antigen is a B cell mitogen and polyclonal B cell activator. © 1985, Gustav Fischer Verlag · Stuttgart · New York. All rights reserved.