There is considerable diversity of opinion as to the nature of the response of depressed patients to amphetamine infusion. The authors report on the clinical response of 18 endogenously depressed patients to double-blind, intravenous administration of amphetamine or saline. Although the drug produced activation, mood elevation, and recall of emotionally charged material in the group as a whole, there was considerable heterogeneity of response as well as a tendency for response dimensions to vary independently of one another. The heterogeneity of clinical response may be associated with differences in underlying clinical, biological, and genetic variables in affectively ill patients.