A B S T R A C T The cytotoxic moiety (ies) in highly purified streptococcal M protein has been shown to be distinct from the type-specific MI determinant. This nontype-specific M-associated determinant (s) (NTSM) causes humoral and cellular immunotoxic responses in man. NTSM1 is common to M\I protein prepared from all streptococcal serotypes studied so far. In this study, immunoabsorbents prepared by entrapping purified MI proteins in polyacrylamide gel were employed to identify, separate, and purify antibodies directed against NTSAM as well as against the type-specific M (TSM) determinants.We found that anti-NTSM\ present in human blood mediated cytotoxic platelet and leukocyte reactions in the presence of "'M proteins" prepared from groups A, C, and G streptococci.