Clonidine hydrochloride and naltrexone hydrochloride, given in combination, were found to provide a safe, effective, and extremely rapid treatment of abrupt withdrawal from methadone hydrochloride therapy. Under controlled inpatient conditions established to assess dosage guidelines and to examine specific signs and symptoms of withdrawal, ten (91%) of 11 patients were able to withdraw completely from methadone therapy by the end of a six-day period. Six days of clonidine hydrochloride treatment, with a peak mean dose of 2.9 mg/day on treatment day 2, attenuated the withdrawal-inducing effects of naltrexone. Naltrexone hydrochloride was gradually increased from an initial 1-mg dose on treatment day 2 to 50-mg maintenance dose on treatment day 5 without an associated increase in withdrawal symptoms. Clonidine significantly decreased BP without producing clinical problems. The withdrawal symptoms of anxiety, restlessness, and muscular aching were most resistant to treatment, but at discharge most patients were completely asymptomatic.