SUMMARY The effects of ouabain, 20 μg/kg, and isoproterenol, 0.03 μg/kg/min, were compared in conscious dogs with acute myocardial ischemia. The animals were instrumented with miniature pressure gauges for measurements of left ventricular (LV) pressure and dP/dt, miniature ultrasonic transducers for measurements of both regional myocardial fiber shortening and ECGs from the same sites and left atrial and aortic catheters for measurements of pressures and regional myocardial blood flow using the radioactive microsphere technique. Coronary occlusion increased heart rate and LV end-diastolic pressure but did not change LV systolic and mean aortic pressures or dP/dt significantly. In the ischemic zone, coronary occlusion reduced systolic segment shortening and blood flow markedly while increasing ST segment elevation. Isoproterenol in the presence of coronary artery occlusion increased heart rate 33 ± 4 beats/min and dP/dt 630 ± 90 mm Hg/sec and decreased mean arterial pressure by 6.3 ± 1.6 mm Hg. In the ischemic zone, isoproterenol reduced flow by 31 + 9.1%, P < 0.01, and increased paradoxical bulging by 0.20 ± 0.07 mm, P < 0.02, and ST elevation by 3.0 ± 0.6 mV, P < 0.01. Ouabain increased dP/dt similarly by 600 ± 90 mm Hg/sec, but did not change heart rate or mean arterial pressure significantly. In contrast to isoproterenol, ouabain increased flow 46 ± 9.2%, P < 0.01, systolic segment shortening 0.35 ± 0.10 mm, P < 0.01, and reduced ST elevation 3.1 ± 0.4 mV, P < 0.01, in the ischemic zone. In conclusion, equi-inotropic doses of ouabain and isoproterenol induced opposite effects on the mechanical function, ECGs and blood flow of severely ischemic tissue. Ouabain appeared to alleviate the ischemic condition, whereas isoproterenol intensified ischemia.