Topical antimicrobial therapy has not been effective in the past against cutaneous bacterial infections. In this study, a new topical antibiotic ointment, mupirocin, was compared with oral erythromycin ethylsuccinate in the treatment of impetigo. Seventy-five patients clinically diagnosed as having impetigo and with positive cultures of Staphylococcus aureus, Streptococcus pyogenes, or both were examined in an investigator-blinded study. Patients used topical mupirocin applied three times daily or the usual oral dose of erythromycin ethylsuccinate (30 to 50 mg/kg per day). Patients' lesions were examined clinically and cultured bacteriologically on days 0, 3, and 8, and 1 week after treatment. Susceptibility testing was performed on pathogens isolated to determine antibiotic resistance. Mupirocin treatment produced similar clinical results to oral erythromycin and was superior in the eradication of S aureus, including antibiotic-resistant S aureus. These results show topical mupirocin to be a safe and effective alternative to oral antibiotic therapy in the treatment of impetigo.