The hypotensive drug clonidine, which stimulates central alpha-adrenergic receptors, was administered to psychiatric patients in a preliminary double-blind study. Two schizophrenic patients became more agitated and aggressive during the trial. The drug showed some antidepressant effects in three of five depressed patients. Clonidine withdrawal appeared to potentiate symptoms in a manic patient. Drug treatment reduced blood pressure and rapid eye movement sleep. Interpretation of behavioral effects of clonidine is limited by uncertainty about the balance of its pre- and postsynaptic effects.