Melatonin is a neurohormone produced by the human pineal gland that plays a role in the regulation of many physiologic processes and has been proposed as a therapy for everything from insomnia to metastatic carcinoma. Melatonin is available in the United States without prescription, and adverse effects appear to be uncommon. However, because melatonin appears to have immunomodulatory properties, the potential exists for the development of autoimmune-related side effects. We describe a patient in whom characteristic clinical and laboratory features of autoimmune hepatitis developed after beginning melatonin therapy for the treatment of insomnia. Liver biopsy demonstrated histologic features of autoimmune hepatitis. Rapid symptomatic and biochemical improvement resulted from the initiation of immunosuppressive therapy; however, hepatitis recurred after the withdrawal of steroid therapy. The temporal relation observed between melatonin use and the development of autoimmune hepatitis raises the possibility that the drug might be involved in the pathogenesis of this patient's autoimmune disease.