Pharmacological blockade of the euphoric effect of amphetamine was studied in amphetamine dependent patients. An eleven grade self-rating scale was used for registration of the subjective feeling of euphoria after intravenous administration of 200 mg d,l-amphetamine. Three neuroleptic drugs, chlorpromazine, thioridazine, pimozide, the α-receptor-blocking agent phenoxybenzamine and the β-receptor-blocking agent propranolol were tested for possible anti-amphetamine effect. — The euphoric effect of amphetamine was significantly reduced after a single dose of 50 mg of chlorpromazine and after 7 and 13 days of chlorpromazine treatment, 50 mg every 8 h. Single doses of chlorpromazine 25 mg or thioridazine 25 and 50 mg, respectively, had no effect. Pimozide significantly reduced euphoria after single doses of 5, 10 and 20 mg, but there was no dose-response relationship. The amphetamine-induced euphoria was also reduced by 7 and 13 days of treatment with pimozide 5 mg daily. Pretreatment for 6 days with phenoxybenzamine had no effect on the response to amphetamine and, propranolol, too both in single doses and after 5 days administration also had no amphetamine blocking effect. — Blood pressure, pulse rate, respiratory rate and body temperature were measured after administration of amphetamine before and after pretreatment with these blocking agents.