A total of 300 Streptococcus pyogenes isolates, collected during 2001 from five hospitals in the Thessalia district (Central Greece), were examined for their resistance to macrolides. Resistance to erythromycin was detected in 58 isolates (19.3%). Of these, 68.9% were susceptible to clindamycin (M-phenotype) and carried the mefA gene. Of the remaining isolates, 18 expressed the MLS(B) phenotype: 12 and six exhibited inducible and constitutive resistance to clindamycin, respectively. All of these strains were found to be ermA(TR) positive, except for four that had the ermB gene. Of the erythromycin-resistant strains, none was found to be resistant to penicillin, tetracycline or quinupristin-dalfopristin. Molecular typing by PFGE showed the presence of a limited number of clones.