After occlusion of a coronary artery in dogs, regionally ischemic myocardium was delineated by means of a strain gauge-tipped, two pronged catheter probe that measures myocardial fiber shortening. The curves of contraction were sensitive to the effects of ischemia. A central zone of complete ischemia was identified as the region in which fiber shortening was lost and replaced by passive fiber lengthening. As the probe was inched away from the center toward the periphery, an intermediate zone of incomplete ischemia was defined as the region in which contractility was partially diminished but not lost. It was assumed that a shift in oxygen balance induced by an intervention will be reflected as a change in contractility of the intermediate zone. Accordingly, the intermediate zone was used as the test zone to evaluate effects of drugs on the extent of regionally ischemic myocardium. Isoproterenol initially augmented contractility of the intermediate zone but, with continued infusion, a secondary reduction in contractility became evident at 30 to 45 minutes. Norepinephrine augmented contractility of the intermediate zone and this effect persisted through the 1 hour observation period. Ouabaln similarly increased the velocity of shortening of the intermediate zone. An increase in left ventricular afterload induced by methoxamine resulted in loss of contractility and its replacement by fiber lengthening in the intermediate zone. These findings indicate that isoproterenol and methoxamine can increase the extent of noncontractlng ischemic myocardium and, hence, infarct size. Norepinephrine and ouabain do not exert this effect.