More than 1100 group A streptococcal isolates collected in the United States (1988-1990) were examined to document an association of individual serotypes with specific clinical infections during the recent resurgence of group A infections and their sequelae. The most commonly isolated strains from patients with only uncomplicated streptococcal pharyngitis ("control" strains) were M serotypes 1, 2, 4, and 12. M1, M3, and M18 were statistically significantly more frequently isolated from patients with serious invasive infections and M3 and M18 from patients with rheumatic fever compared with the distribution of serotypes from the 866 control strains. An unexpected and important finding indicated that isolation rates of M1 streptococci varied geographically within the United States by year. The propensity for M1 streptococci to be statistically associated with severe systemic infections appeared unrelated to the M1 isolation rates from patients with only uncomplicated pharyngitis, thus offering additional support for the concept of strain-associated virulence rather than virulence broadly related to a given serotype.