Clonidine hydrochloride was found to be effective in the treatment of methadone hydrochloride withdrawal. Under controlled inpatient conditions established to assess dosage guidelines and to examine specific signs and symptoms of withdrawal, 20 of 25 (80%) patients were able to withdraw completely from methadone by the end of a two-week period. In most patients, ten to 11 days of clonidine administration, with a peak mean dose of 16 micro g /kg/day, resulted in a perceived reduction in symptoms compared with previous attempts to become opiate free. At these doses clonidine significantly reduced standing blood pressure without producing clinical problems. The withdrawal symptoms of anxiety, restlessness, insomnia, and muscular aching were most resistant to clonidine treatment and were reported by the majority of patients.