The efficacy of erythromycin base (E-Mycin tablets, 333 mg) and the efficacy of tetracycline hydrochloride (Panmycin tablets) were compared in this double-blind, randomized study. Two hundred patients with moderate to moderately severe acne vulgaris were randomly assigned to the study. One hundred patients received 1 gm of erythromycin base by mouth per day for 4 weeks, followed by 333 mg/day for 8 weeks, plus placebo for tetracycline. The second group of patients received 1 gm of tetracycline by mouth per day for 4 weeks, followed by 500 mg/day for 8 weeks, plus placebo for erythromycin. Both drugs reduced acne severity to the same extent. Pustules, papules, and open comedo counts decreased significantly over the 12-week period. Seventy-seven percent of the erythromycin-treated patients and 89% of the tetracycline-treated patients stated that their acne was markedly improved or improved by week 12. Most of the side effects in patients treated with erythromycin were gastrointestinal symptoms. Among the side effects in patients treated with tetracycline were Candida vaginitis in one patient and pseudotumor cerebri in one patient.