During the 1980s there was a resurgence of serious Streptococcus pyogenes infections with complications, including rheumatic fever, sepsis, severe soft-tissue invasion, and toxic-shock-like syndrome (TSLS). We have investigated the suggested association between expression of a scarlet fever toxin, SPE A, and systemic toxicity, and the possibility that a new highly virulent clone of S pyogenes has emerged and spread world wide. We studied serotype M1 strains, the serotype most commonly associated with serious complications. 19 isolates from patients with sepsis, with or without TSLS, and 48 from patients with uncomplicated pharyngitis or superficial skin infection were subjected to restriction-enzyme digestion and electrophoresis; 56 isolates (19 serious, 37 uncomplicated disease) were then examined by hybridisation to an speA gene probe. 17 (90%) of the 19 serious-disease isolates had a characteristic ("invasive", I) restriction-fragment profile and were positive for the speA gene. Significantly lower proportions of the isolates from patients with uncomplicated disease had the I profile (21/48 [44%]; p=0·0035) and speA (20/37 [54%]; p<0·001). These findings suggest that the strains from patients with serious disease are a unique clone, which became the predominant cause of severe streptococcal infections in the United States and elsewhere in the late 1980s.