Combined clonidine and naltrexone treatment allowed 38 of 40 patients addicted to methadone to withdraw completely in 4-5 days. For most patients naltrexone was gradually increased from 1 mg/day to 50 mg/day over 4 days. Clonidine reduced the intensity of naltrexone-induced withdrawal symptoms. Clonidine significantly decreased blood pressure without producing syncope and caused sedation but no other clinical problems. The withdrawal symptoms of anxiety, anorexia, insomnia, restlessness, and muscular aching were most resistant but were mild or nonexistent at discharge. Clonidine-naltrexone treatment should succeed with patients receiving methadone doses up to 50 mg/day, facilitate naltrexone maintenance, and apply to many clinical settings.