The M protein on the surface of Streptococcus pyogenes cells enables the organisms to resist ingestion and killing by phagocytic cells in the blood of the non-immune host. In the immune host, type-specific antibodies against the M protein neutralize the antiphagocytic effect and allow the rapid elimination of any invading streptococcci having the same serotype of M protein. Recent studies¹ in our laboratories of the primary structure of one of these M proteins (type 24) have indicated that the molecule is composed of repeating covalent structures, each of which contains protective antigenic determinants. These results suggest that only a small portion of the M protein molecule may be required to produce primary protective immunity against S. pyogenes. We now report that this notion is well founded. Our findings may have a bearing on the development of M-protein vaccines to protect against streptococcal infections causing acute rheumatic fever and rheumatic heart disease².