The effectiveness of amantadine hydrochloride was evaluated in a double-blind placebo controlled drug trial. The subjects were 42 cocaine dependent men enrolled in a day hospital program. Twenty-one patients were prescribed 100 mg/bid of amantadine to be taken over 10.5 days and 21 were prescribed an equivalent amount of placebo. The primary outcome measures were the Addiction Severity Index at 1 month after study entry and urines during the drug trial (end of weeks 1 and 2) and 1 month after study entry. Urines obtained at the end of the drug trial (2 weeks) indicated that the subjects receiving amantadine (93%) were more likely (P = 0.040) to be free of cocaine than the placebo (60%) subjects. Urine toxicology data at 1-month follow-up again indicated that more of the amantadine subjects (83%) were free of cocaine than the placebo (53%) subjects (p = 0.049); although no differences were found in self-reports of cocaine or other substance use in the past 30 days. The urine findings provided preliminary indication that amantadine may have some effectiveness in reducing cocaine use in cocaine dependent patients.