A prospective evaluation of the efficacy and safety of oral ibuprofen and tetracycline hydrochloride was conducted for 8 weeks in patients with moderately severe acne. Sixty-eight patients were randomly assigned in a double-blind fashion to one of four regimens: (1) one 600 mg ibuprofen tablet plus one 250 mg tetracycline capsule four times daily; (2) one 600 mg ibuprofen tablet plus one placebo capsule four times daily; (3) one 250 mg tetracycline capsule plus one placebo tablet four times daily; and (4) one placebo tablet and one placebo capsule four times daily. Sixty patients completed the 8-week study. The mean percent improvement in the groups treated with ibuprofen and tetracycline (56% +/- 5 SE), ibuprofen alone (26% +/- 13 SE), or tetracycline alone (26% +/- 9 SE) was statistically significant. However, only the combination of ibuprofen and tetracycline therapy had an effect statistically better than the placebo response (16+ +/- 11 SE). Adverse effects were transient and were similar in all four groups.