A double-blind, 12-week study was undertaken to determine the safety and efficacy of a formulation of 4% erythromycin plus 1.2% zinc acetate compared with its vehicle. The study was continued for 40 weeks after the 12-week double-blind phase by switching vehicle-treated patients to active treatment and continuing to give patients treated with active drug the same treatment. Seventy-three female patients started the study; 39 completed 1 full year of study. In the first 12 weeks statistically significant differences were noted in the efficacy of the erythromycin-zinc compared with vehicle for acne severity grades (global assessment) and for papule, pustule, and comedo counts. After crossover, the vehicle-treated group receiving active therapy duplicated the improvement of the group initially treated with erythromycin-zinc. No clinical problems with superinfection or secondary infection occurred during 1 year of treatment in 39 patients.