ET-495, a putative central dopamine receptor stimulant, was given to endogenously depressed individuals, all of whom were largely unresponsive to previous drug treatment. The drug exhibited a rapid and, in some cases, a pronounced antidepressant effect. This effect was short-lived, however, and, within a brief period, depression returned accompanied by a consistent syndrome of anger, irritability, hostility and poor temper control. In one individual. with a bipolar history, the induction of a paranoid psychosis and auditory hallucinosis occurred. While the data suggest a role for dopamine in the symptomatic relief of depression in man, they also imply that this monoamine cannot, in and of itsel·f, be considered as the primum movens in either the action of other (established) antidepressant drugs, or as underlying depressive illness