Oxygen utilization, arterial and venous blood gas levels, hemodynamic values and exercise tolerance were compared before and after administration of propranolol and verapamil in 10 patients with stable angina pectoris. During exercise, propranolol decreased cardiac output (CO) by 22%; O2 extraction was increased and O2 consumption (VO2) did not change. With verapamil treatment, CO modestly increased (7%), O2 extraction decreased and VO2 did not change. In contrast to O2 utilization, the drugs produced opposite changes in mixed venous and arterial blood gas levels. Propranolol decreased mixed venous pH, increased CO2 tension and decreased the pH of arterial blood. Verapamil increased venous pH and decreased CO2 tension; pH of arterial blood did not change. The drugs yielded similar levels of antianginal efficacy, but patients exercised longer during verapamil therapy and were less fatigued. The hemodynamic and metabolic differences suggest that muscle perfusion during exercise influences the onset of fatigue and may help determine the choice of therapy.