The clonal relationships among 261 erythromycin-resistant Streptococcus pyogenes isolates collected in 1986-1997 from nine countries in Europe and North and South America were studied by using two molecular typing methods: Vir typing and random amplified polymorphic DNA (RAPD) analysis. A total of 49 different Vir genotypes (VTs) and 33 different RAPD patterns were noted among the 261 isolates. Isolates that shared the same VT and RAPD pattern were considered to belong to the same clone. Although as many as 60 different clones were found among the isolates studied, only seven clones, comprising 157 of the 261 (60%) isolates, were found in more than one country. Five of these seven clones expressed the M phenotype known to be associated with the drug efflux mechanism, and only two clones expressed the macrolide-lincosamide-streptogramin B-resistance phenotype. The results indicate a polyclonal spread of erythromycin-resistant Streptococcus pyogenes. Furthermore, predominance of the seven clones indicates that erythromycin-resistant Streptococcus pyogenes of the same clonal origin may be widely distributed and found in several different countries.