A molecular epidemiology analysis was performed with over 440 clinical isolates of Streptococcus pyogenes obtained from 11 different countries in order to determine the frequency of occurrence of the type A streptococcal exotoxin (erythrogenic toxin) gene (speA) among group A strains. The colony hybridization technique employing a specific internal fragment of the speA gene was used for initial screening, and all positive results were further confirmed by the Southern hybridization technique. Among over 300 general strains obtained from patients with a variety of diseases, except scarlet fever (such as tonsillitis, impetigo, cellulitis, pyoderma, abscess, rheumatic fever, and glomerulonephritis), 15% were found to contain the speA gene. Among a group of 146 strains obtained from individuals described as having scarlet fever, 45% were shown to contain the speA gene. Further analysis of the data indicated that strains with certain M- or T-type surface antigens showed a higher (such as M and T types 1 and 3/13) or lower (such as M2, M12, T4, T5, and T28) tendency to contain the speA gene. No correlation was found between speA content of a strain and the ability to cause a specific disease, although strains possessing the speA gene were more likely to be associated with scarlet fever and rheumatic fever than with other types of disease.