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Because of the recent resurgence of Group A streptococcal infections and their sequelae and to concerns about Group A streptococcal antimicrobial resistance, 282 isolates from acute pharyngitis and 43 additional isolates from severe, invasive infections were examined for susceptibility to 11 oral antibiotics. M serotypes 1, 2, 3, 4 and 12 accounted for more than one-half of the pharyngeal isolates; M serotypes 1 and 3 accounted for most isolates from severe infections. All 325 isolates were exquisitely susceptible to penicillin (Concentration of antibiotic required to inhibit 90% of isolates, 0.012 μg/ml). Only approximately 4% of the tested strains demonstrated an erythromycin minimum inhibitory concentration of 0.5 μg/ml or greater; the new macrolides, azithromycin and clarithromycin, were similar. The cephalosporins varied somewhat in their ability to inhibit Group A streptococci, but all were effective in vitro. No major differences in minimum inhibitory concentrate were observed between strains associated with severe infections and those from uncomplicated upper respiratory tract infections. On the basis of the 325 isolates examined, we conclude that antimicrobial resistance has not been a factor in the recent resurgence of Group A infections.