We conducted a double-blind, controlled trial of low-dose (150 mg/d) oral clindamycin hydrochloride vs placebo to prevent recurrent staphylococcal skin infections. Twenty-two patients (11 in both the placebo and clindamycin treatment groups) completed the trial and were assessable. The two groups did not differ as to age, sex, race, or the number of recurrent abscesses preceding the trial. In pretrial evaluations, no patient had hypogammaglobulinemia or abnormal neutrophil function. Sixty-four percent (7/11) of the placebo-treated patients had a recurrent abscess within three months of enrollment whereas 82% (9/11) of the patients treated with clindamycin were free of any infection during the three-month treatment period. Of the nine patients who responded to clindamycin treatment, six did not have a recurrent infection for at least nine months after discontinuing antibiotic therapy. All patients tolerated the regimen without side effects. We conclude that a three-month course of low-dose oral clindamycin is an effective, convenient, well-tolerated, and often durable approach to prevention of recurrent staphylococcal skin infections.