Staphylococcus aureus has been consistently isolated from a high proportion of impetiginous lesions, and in several recent studies, it was present in the majority of the cases. Since recently a large proportion of S. aureus strains in our community showed erythromycin resistance, we undertook a prospective double-blind controlled study comparing topical mupirocin with oral erythromycin to determine (i) the prevalence of erythromycin-resistant S. aureus strains in impetigo and (ii) whether an increased rate of failure of erythromycin treatment was associated with such resistance. A total of 102 patients 3 to 185 months old (median = 49 months) were enrolled. Culture was positive for 97 of 102 (95%) patients, and S. aureus was present in 93% of the patients for whom cultures were positive. S. aureus was the single pathogen in 64% of these patients. Erythromycin-resistant S. aureus strains were present in 27 of 91 (28%) patients for whom cultures were positive. In all cases but one, S. aureus was resistant to penicillin, and in all cases it was sensitive to mupirocin. A marked difference was observed in favor of mupirocin in the clinical courses of the disease. However, only patients with erythromycin-resistant S. aureus strains had unfavorable courses compared with those treated with mupirocin (failure rate, 47 versus 2%, respectively). Patients with erythromycin-susceptible S. aureus strains who received erythromycin had a failure rate of 8%. In four patients, S. aureus strains initially susceptible to erythromycin became resistant during treatment. We conclude that erythromycin-resistant S. aureus strains are commonly isolated from impetigo in our region.(ABSTRACT TRUNCATED AT 250 WORDS)