To assess the effects of oral bepridil therapy (10-14 days) on cardiac performance and myocardial energetics in the presence of depressed left ventricular function, systemic and coronary hemodynamic effects and neurohumoral effects were evaluated in 7 patients with coronary artery disease and reduced ejection fraction at control, submaximal, and maximal pacing rates during atrial pacing stress. After bepridil therapy, arterial, right atrial, and left ventricular filling pressures as well as systemic vascular resistance and left ventricular stroke work index did not change, suggesting no deleterious effects of bepridil on cardiac performance in patients with reduced ejection fraction. Rate-pressure product, myocardial oxygen consumption, coronary sinus blood flow, myocardial lactate extraction, and catecholamine balance remained unchanged. Development of angina during pacing showed a variable response to bepridil. We conclude that despite its potential negative inotropic effect, bepridil does not exert deleterious effects on hemodynamics or left ventricular performance. The mechanism for its beneficial antianginal effect may be due to favorable redistribution of myocardial blood flow to ischemic zones; no clear effect on anginal threshold or sympathetic tone could be demonstrated in these patients.