Previous studies of the effect of tricyclic antidepressants on left ventricular function in depressed patients with moderate to severe ventricular impairment have focused primarily on imipramine hydrochloride. In a prior study, we found that although imipramine had no effect on ejection fraction as measured by first-pass radionuclide angiography, the treatment could not be tolerated by 50% of the patients because of intolerable drug-induced orthostatic hypotension. Nortriptyline hydrochloride is an effective antidepressant that, in depressed patients without heart disease, causes significantly less orthostatic hypotension than imipramine. To see if this advantage could be safely extended to patients with congestive failure, we measured the effect of nortriptyline on ejection fraction and blood pressure in 21 depressed patients with left ventricular impairment. Ejection fraction was unchanged by nortriptyline treatment, and orthostatic hypotension developed in only one (5%) of 21 patients. Nortriptyline emerges as a relatively safe treatment for depression in patients with left ventricular impairment.