In humans, reflex sympathetic nerve activation modulates the direct cardiac action of nifedipine after systemic administration and results in a positive chronotropic and inotropic response. The coronary hemodynamic and metabolic effects of nifedipine were evaluated after propranolol-induced acute beta-receptor blockade in 12 patients with angiographically documented coronary artery disease. The intravenous injection of propranolol led to a decrease in heart rate, coronary blood flow and myocardial oxygen consumption and an increase in coronary vascular resistance and the coronary arteriovenous oxygen difference. Mean aortic pressure did not change. The subsequent intravenous administration of nifedipine resulted in a transient increase in coronary blood flow and a reduction in coronary vascular resistance and the coronary arteriovenous oxygen difference and a sustained decrease in mean aortic pressure and myocardial oxygen consumption without significant changes in heart rate. Thus, in the presence of beta-receptor blockade, the positive chronotropic response to nifedipine is attenuated and nifedipine reduces myocardial oxygen consumption significantly. The vasodilatory effect of nifedipine is maintained and a potential propranolol-related inappropriate vasoconstriction may be reversed. The combination of nifedipine and beta-receptor blocking agents may be useful in the treatment of patients with both effort-induced angina and angina related to changes in coronary vasomotor tone.