An antigen that cross reacts with mammalian heart tissue has been shown to be present in several strains of S mutans. Inoculation of S mutans into rabbits elicited heart-reactive antibody as part of the immunologic response. This heart-reactive antibody was demonstrated to be tissue-specific in that it only bound heart and smooth muscle tissue. Similar results have been previously reported using group A streptococci. Adsorption studies using sarcolemmal sheaths, group A streptoccal membranes, and fractions of cariogenic streptococci demonstrated the presence of a similar antigen. The aforementioned fractions could remove heart-reactive antibody from both immune rabbit serums and serums from patients with acute rheumatic fever. These findings dictate the necessity for testing any future caries vaccine containing fractions of S mutans for the presence of this cross-reactive antigen to avoid a possible autoimmunization.