Production of opacity factor (OF) by 841 pharyngeal isolates of group A streptococci from schoolchildren in Casper, Wyoming was studied along with T- and M-typing of the streptococcal strains. The majority (89%) of M-typable strains were OF-negative in contrast to M-nontypable isolates, 45% of which were OF-positive. There was no apparent relation between the production of OF by the M-nontypable isolates and the type of infection (symptomatic vs. asymptomatic), degree of positivity of initial culture, antistreptolysin O response, and failure to eradicate the organisms by treatment with antibiotics. However, seasonal shifts in the prevalence of M-nontypable OF-positive strains provided evidence of change in streptococcal ecology, such a shift would not have been detected by T-typing alone. Thus, OF production is an additional epidemiologic marker that is helpful in differentiating M-nontypable group A strains that bear common T-antigens.