The effects of practolol, a new beta-adrenergic blocking agent, and propranolol were studied in volunteers. At rest, practolol caused a very small reduction in cardiac index (CI), 190 ml,P< 0.25, and preejection period (PEP) lengthened 3 msec,P< 0.025. In contrast, propranolol caused a reduction in CI of 770 ml,P< 0.001. Heart rate (HR) slowed 10 beats/min,P< 0.001, stroke volume index (SVI) fell 6 ml,P< 0.005, PEP lengthened 16 msec,P< 0.001, and peripheral vascular resistance (PVR) increased 419 dynes-sec-cm−5,P< 0.001. Practolol reduced the increase in CI caused by an isoproterenol infusion by 65%,P< 0.005, by blocking the increase in HR by 73%,P< 0.05. Practolol also reduced the shortening of PEP and LVET caused by isoproterenol. PVR decreases due to isoproterenol were not blocked by practolol although they were slightly attenuated,P< 0.025. Practolol reduced the increase in CI caused by exercise by 22%,P< 0.05, by blocking the increase in HR by 29%,P< 0.01. Practolol also reduced the increase in tension-time index due to exercise by 25%,P< 0.025.Practolol has little effect on the performance of the normal heart at rest. It does block the cardiac effects of isoproterenol and exercise, largely through chronotropic mechanisms. The reductions in pressure-time relationships with exercise indicate reduced oxygen consumption by the heart, and therefore imply a therapeutic benefit in exercise-induced angina.