Fourteen patients with severe, treatment-resistant, nodulocystic acne have been treated with 13-cis-retinoic acid in a double-blind study. The patients were treated with either 0.1, 0.5, or 1.0 mg/kg/day of 13-cis-retinoic acid for 12 weeks. A marked dose-related decrease in sebum production, which was usually evident within 2 weeks of the onset of therapy, was observed in all patients. At a dose of 1.0 mg/kg/day of 13-cis-retinoic acid, sebum production was decreased to about 10% of the pretreatment value. Clinical improvement, as judged by counting the nodulocystic lesions and measuring their greatest diameters, was noted in all three groups. The most common clinical side effects were cheilitis, desquamation of the skin, and pruritus, but the side effects were not severe enough to require interruption of treatment. Laboratory abnormalities during therapy were minimal and also did not necessitate the cessation of therapy.