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The systemic and coronary hemodynamic effects of relatively large doses of propranolol have been studied following its infusion into intact anesthetized dogs at rest and during simulated exercise. At rest, the administration of propranolol was associated with decreased cardiac output and ventricular work and increased peripheral, pulmonary, and coronary vascular resistances. Coronary blood flow and coronary sinus oxygen content decreased while myocardial oxygen consumption and the index of cardiac efficiency were unchanged. The usual hemodynamic response to mild exercise was obtained, with increased cardiac output, cardiac work, body oxygen consumption, and a modest but insignificant increase in coronary blood flow. When propranolol was given and the same exercise continued, body oxygen consumption, cardiac output, and left ventricular work significantly decreased. Insignificant decreases occurred in coronary blood flow, left ventricular oxygen usage, and coronary sinus oxygen content. The present observations are consistent with the thesis that beta-adrenergic blockade induced by propranolol decreases cardiac work at rest and reduces the cardiovascular response to exercise.