Antigens extracted from cells of Streptococcus pyogenes T6 and Streptococcus mutans strains AHT, BHT, 10449, OMZ175, and K1R adsorbed to the sarcolemmal sheath of cardiac muscle cells in vitro. Similar preparations from S. salivarius, S. sanguis, Staphylococcus aureus, and Lactobacillus casei had weak or negligible tissue-binding activity. Tissue-bound bacterial antigens were detected with homologous rabbit antisera with both indirect immunofluorescence tests and an indirect radioimmunoassay. Serological cross-reactivity was observed between the tissue-binding factors of S. pyogenes and S. mutans cells but not between the bacteria and muscle tissue. In a comparative study of extraction procedures, the greatest yield of tissue-binding factors was obtained from group A streptococci by cell disruption in buffer at 40C. Hot aqueous phenol and hot water extracts were inactive. Antibodies specific for the tissue-binding factor(s) were readily adsorbed from rabbit anti-S. pyogenes serum by a preparation of isolated cytoplasmic membranes but not by a suspension of cell wall fragments. The heart-binding component of S. pyogenes cell extracts was inactivated by protease digestion and heat treatment and to a lesser extent by periodic acid oxidation. The capacity of heart cell components to adsorb streptococcal antigens was reduced by protease treatment but not by the action of neuraminidase, hyaluronidase, organic solvents, or detergents. Streptococci have been shown to selectively adhere to epithelial cells (1-3, 8, 39), tooth surfaces (23, 24), and salivary components (11, 21, 22, 30) of the human oral cavity. These studies suggest that this phenomenon plays a fundamental role in the colonization of oral surfaces by these bacteria and, consequently, the pathogenesis of certain diseases including streptococcal pharyngitis and dental caries (for review, see 20, 24, 38). The mechanisms) by which streptococci ad-'Titers (IIF) from each of three rabbits immunized with the bacterium. S. aureus titer was determined by agglutination.