Accumulated evidence indicates that lipoteichoic acid (LTA) is centrally involved in the attachment of group A streptococci to epithelial cells of the host. The binding of LTA to a variety of host cells is mediated by the glycolipid end of the LTA molecule, which can form ionic complexes with streptococcal surface proteins, permitting the reorientation of the LTA to expose some of its lipid ends toward the surface of the organism. The ability of albumin to block the adherence of streptococci to epithelial cells and to bind to LTA-M protein but not deacylated LTA-M protein complexes supports the idea that the lipid ends remain free to interact with cell membrane receptors. The cell membrane receptors appear to consist of a lipid-binding region(s) on fibronectin molecules on the surfaces of oropharyngeal epithelial cells. Although streptococci exhibit LTA-sensitive binding to phagocytic cells in a serum-free system, in the presence of serum, they do not; rather, complement bound to the streptococcal cell surface is required for recognition by phagocytes. The binding of fibrinogen to the M protein on the surface of M-rich streptococci specifically blocks the recognition of the organisms by opsonic complement components. The attachment of M-rich streptococci to phagocytic cells requires the development of antibodies directed specifically toward regions of M protein not blocked by fibrinogen.