Despite extensive evidence that selective dopamine antagonists attenuate the reinforcing effects of stimulants in laboratory animals, there is little evidence that dopamine antagonists block the positive subjective effects of stimulants in humans. However, recent evidence suggests that the subjective effects of stimulants in humans may depend in part on serotonin. The goal of this study was to examine the effects of haloperidol, a drug that primarily blocks dopamine receptors, and risperidone, a drug that blocks both dopamine and serotonin receptors, on the physiological and subjective effects of methamphetamine in healthy volunteers. Two groups of subjects participated in a placebo-controlled, within-subject, 2 x 2 repeated measures design. One group was tested with haloperidol (3 mg; N = 18), the other with risperidone (0.75 mg; N = 18). Each subject participated in four sessions receiving all combinations of antagonist or placebo and methamphetamine (20 mg) or placebo. Dependent measures included vital signs and standardized questionnaires of subjective effects. At these doses, both haloperidol and risperidone produced mild sedative-like effects compared to placebo. However, neither drug consistently reduced the stimulant-like effects of methamphetamine. These results add to the growing body of literature suggesting that D(2) dopamine receptor antagonists do not block the euphorigenic subjective effects of stimulant drugs in humans, and also do not support the idea that serotonin contributes significantly to these effects.