The subjective, behavioral, and physiological effects of bupropion, a nontricyclic antidepressant, were compared with those of dextroamphetamine and placebo in a randomized double-blind crossover study. The volunteers who participated were multiple-drug abusers. Six acute drug treatments, three doses of bupropion (100, 200, 400 mg), two doses of dextroamphetamine (15, 30 mg), and placebo were administered orally at intervals of not less than 72 h. Results indicated that the subjective effects of amphetamine as measured by the Addiction Research Center Inventory (ARCI) differed markedly from bupropion and placebo. Bupropion, in contrast to amphetamine, had no peripheral sympathomimetic effects and did not reduce appetite or caloric intake.