An apparently allergic reaction manifested by exfoliative dermatitis, mucous membrane desquamation, eosinophilia, severe hepatitis, and death occurred in an 80-year-old woman after therapy with imipramine hydrochloride and desipramine hydrochloride. Autopsy showed massive central and midzonal hepatic necrosis. To the authors' knowledge this is the first report of a lethal hepatic hypersensitivity reaction following administration of these drugs.