A clinical trial of minocycline in a total of 10 patients with previously untreated lepromatous leprosy was conducted in order to evaluate the efficacy of a single, initial, 200-mg dose and 100 mg twice daily of minocycline for a total duration of up to 3 months. Patients improved remarkably quickly. Although single-dose therapy did not result in a significant killing of Mycobacterium leprae, viable M. leprae were cleared from the dermis regularly by 3 months of twice-daily therapy, a rate similar to that achieved by minocycline 100 mg once daily. Because more side effects were noted herein than previously with 100 mg daily, we recommend that minocycline, when applied, be administered at 100 mg daily to leprosy patients.