The purpose of our study was to determine the prevalence of macrolide resistance in 3,188 pharyngeal Streptococcus pyogenes isolates collected at the Institute of Public Health of Serbia during the period 2006-2008. The disk diffusion tests were used to determine the susceptibility of the isolates. Two hundred and sixteen S. pyogenes isolates (6.8%) were resistant to erythromycin, with 9 isolates coresistant to tetracycline: 181 isolates harbored mefA gene, 19 ermB gene, 11 ermA(TR) gene, 5 ermB and mefA genes, and 7 tetM gene. Although the prevalence of macrolide resistance in pharyngeal S. pyogenes isolates is low in Serbia, monitoring of the emergence of resistance is advisable.