The efficacy and side effects of topical mupirocin (Bactroban) and fusidic acid (Fucidin) ointment were compared in a double-blind, randomized trial in 70 patients who came to the Dermatologic Clinic of L'Enfant Jésus Hospital with primary or secondary (or both) skin infections. Thirty-five patients were treated with mupirocin and 35 patients were treated with fusidic acid three times a day for seven days. Clinical and bacteriologic assessments were conducted before and after treatment. The efficacy of mupirocin, in terms of resolution and improvement of clinical signs and symptoms of infection, as well as of the elimination of infecting organisms, was similar to that of fusidic acid. Of 34 patients (1 could not be evaluated) treated with mupirocin, a clinical cure was achieved in 18, and significant improvement was demonstrated in 15. Similarly, of 35 patients treated with fusidic acid, a clinical cure was achieved in 18 and improvement occurred in 15. Bacteriologic cure rates were 97% (30 of 31 patients evaluated) in the mupirocin-treated group, compared with 87% (27 of 31 patients evaluated) in the fusidic acid-treated group. No side effects were observed in either treatment group. Because topical 2% mupirocin has little or no potential for irritation, systemic side effects, or cross-resistance with other antibiotics, its efficacy is likely to make this new compound a useful agent for the treatment of superficial skin infections.