A group of 135 college students with acne was evaluated in a 12-week, double-blind study comparing placebo, oral tetracycline 0.5 gm daily, and a new topical tetracycline preparation. The topical tetracycline preparation containing n-decyl methyl sulfoxide to enhance penetration, produced statistically significant improvement of acne as compared to placebo after 7, 10, and 12 weeks of treatment. Oral tetracycline, 0.5 gm daily, was statistically significantly more effective for acne than placebo after 4, 7, 10, and 12 weeks of therapy. The placebo group also had marked improvement which may have been related to sun exposure. Emotional stress produced by final examinations had no apparent effect on the patients given placebo, oral, or topical tetracycline. Side effects of the topical tetracycline included a slight yellowish discoloration of the skin in 25% of the subjects and transient stinging or tingling sensation after application in 36%.