Previous studies have shown that the streptococcal hemolysin, streptolysin S, is capable of interacting with hydrogen peroxide (H2O2) to injure vascular endothelial cells (Free Radic. Biol. Med. 7:369-376; 1989). To extend these observations, intact group A streptococci (strain 203S) were examined for ability to injure endothelial cells alone and for ability to injure the same cells in the presence of sublethal concentrations of H2O2 (generated from glucose/glucose oxidase). While neither control bacteria nor bacteria that had been pretreated with poly-L-histidine to render them cationic were cytotoxic to endothelial cells by themselves under the conditions of the experiment, endothelial cells were injured by combinations of streptococcal cells and sublytic amounts of H2O2. Taken together, these data suggest that the sequelae which often occur following primary infection with group A streptococci may be the result of a combined assault of host inflammatory cells and the invading bacteria on the vascular lining cells of the host.