The reinforcing properties of amphetamine were assessed in two groups of subjects for whom the drug was hypothesized to be a more effective reinforcer than for control subjects. Preference for amphetamine (5 and 10 mg) over placebo was evaluated in subjects who were concerned about being overweight (n = 13), in subjects with depression (n = 15), and in control subjects (n = 25). Subjective effects of the drugs were measured by self-report questionnaires. All three groups chose 5 mg d-amphetamine as often as they chose placebo. The control and weight-concern group chose 10 mg d-amphetamine significantly more often than placebo. Neither the choice behavior nor the subjective effects of the drug indicated that amphetamine was a more effective positive reinforcer in the experimental groups, because of either its anorectic properties or its presumed antidepressant properties. The results are discussed in terms of the relative risk for stimulant abuse in populations with these characteristics.