To determine whether the association of nicardipine with propranolol had additive effects on myocardial metabolism, 16 patients with angina pectoris were studied invasively before and after 1 month of therapy with a combination of nicardipine and propranolol and compared to a group of 42 patients treated with nicardipine (n = 17) or propranolol (n = 25) alone. When data were compared at a fixed heart rate (atrial pacing), mean blood pressure was reduced with combined treatment from 96 ± 19 to 76 ± 13 mm Hg (p < 0.003). Myocardial oxygen uptake and coronary sinus flow decreased significantly from 20 ± 9 to 14 ± 6 ml/min (p < 0.015) and from 152 to 111 ml/min (p < 0.05), respectively. The arterio-coronary sinus difference in oxygen content also decreased (13.3 to 12.5 ml/dl; p < 0.0025), suggesting an improved balance be ween oxygen supply and demand. Such changes in coronary blood flow and myocardial oxygen uptake were not observed in the group of patients assigned to monotherapy. Lactate uptake rose and the abnormal glutamine production, which worsened with propranolol monotherapy, improved with nicardipine and propranolol (-2.0 to -1.4 μmol/min; p < 0.05 vs propranolol). The superiority of nicardipine and propranolol over propranolol monotherapy was maintained during a pacing stress test. Thus the combination of nicardipine with a beta blocker had greater oxygen-sparing effects and restored aerobic metabolism better than either drug alone, allowing optimal use of the coronary reserve.