OBJECTIVE The cardiovascular effects of therapeutic plasma levels of tricyclic antidepressants in depressed patients with and without preexisting cardiac disease have been well characterized and include orthostatic hypotension and conduction delay. Bupropion, structurally unrelated to tricyclic antidepressants, is relatively free of cardiac side effects in depressed patients without cardiac disease. However, it is unknown whether bupropion is safe for depressed patients with preexisting heart disease, so the authors studied the cardiovascular effects of bupropion in such patients. METHODS The subjects were 36 inpatients with DSM-III major depression and preexisting left ventricular impairment (N = 15), ventricular arrhythmias (N = 15), and/or conduction disease (N = 21). The patients continued their cardiac drug regimens and received bupropion for 3 weeks (mean +/- SD dose = 442 +/- 47 mg/day). Cardiovascular functioning was measured by pulse, blood pressure, high-speed ECG, 24-hour portable ECG, and radionuclide angiography. RESULTS Although bupropion caused a rise in supine blood pressure, it did not cause significant conduction complications, did not exacerbate ventricular arrhythmias, had a low rate of orthostatic hypotension, and had no effect on pulse rate. However, bupropion treatment was discontinued for 14% of the patients because of adverse effects, including exacerbation of baseline hypertension in two patients. CONCLUSIONS The cardiovascular profile of bupropion may make this drug a useful agent in the treatment of the depressed patient with preexisting cardiovascular disease. Further studies, with longer durations of bupropion treatment and more subjects, are needed to confirm these findings.