Streptococcus pyogenes is the most prevalent cause of tonsillopharyngitis in children. The drug of choice for infections caused by this microorganism is penicillin. The problem of treating such infections arises when erythromycin-resistant strains occur. The aim of the study was to determine the prevalence of Streptococcus pyogenes resistant to erythromycin. The organism was recovered from the pharynx of children hospitalized or treated on outpatient basis at the University Children?s Hospital in Belgrade. Streptococcus pyogenes was identified on blood agar, using bacitracin disc, and confirmed by latex agglutination test (Slidex bioMerieux). Disc diffusion test was carried out to estimate the penicillin resistance. Erythromycin disc was used as screening method to detect erythromycin-resistant Streptococcus pyogenes. MIC for erythromycin was performed by broth dilution method. In the study period from January 2001 to December 2003, all 1100 isolates of Streptococcus pyogenes had usual level of penicillin sensitivity. In 2001, only 0.45% of isolates were erythromycin-resistant. In 2002, erythromycin resistance was 0.63%, while in 2003, it was 1.09%. MIC for erythromycin was from 1 to 128 mg/l. Three strains had constitutive and one strain had inducible resistance to clindamycin. According to the results, our conclusion is that, despite sensitivity to penicillin, resistance to macrolides is the emerging phenomenon. Reasonable use of macrolide antibiotics is necessary to maintain the resistance at the lowest level.