The relation of streptococcal cell products to pathogenicity of the group A streptococci has been the subject of many investigations and has led to the realization that no single extracellular or intracellular component can be equated to the virulence of these organisms. However, there is considerable evidence to establish type-specific M antigen as the most important virulence factor of group A streptococci. The literature regarding the preparation and properties of M antigen and its role as a virulence factor has recently been reviewed by Lancefield (1962). That M antigen is a major virulence factor is based largely upon indirect evidence. Strains virulent for mice and resistant to phagocytosis generally contain M antigen. Blocking M antigen with specific antibody or removing it enzymatically results in a decrease in virulence or in resistance to phagocytosis. Furthermore, mice can be protected against virulent group A streptococci with homologous anti-M serum. In the present study we investigated, by a more direct approach, the role of M protein as a virulence factor. Essentially, acid extracts of M protein were