Hemodynamic and regional myocardial blood flow responses were studied 5 seconds (early) and 30 seconds (late) after abrupt proximal aortic constriction in chronically instrumented awake dogs. During the early phase, left ventricular end-diastolic pressure (LVEDP) increased and stroke volume (SV) decreased significantly. During the late phase, there was a positive inotropic response manifested by a decrease in LVEDP and increase in SV (Anrep effect). The late inotropic response was closely associated with a recovery from subendocardial underperfusion. Hemodynamic and regional flow responses after beta-adrenergic blockade with propranolol (0.4 mg/kg) were similar to those observed during control. Studies during coronary vasodilation induced by adenosine (0.75--1.0 mg/kg per minute) showed that, if subendocardial flow was elevated during the early phase, the early increase of LVEDP and decrease of SV were less than control; however, if subendocardial flow did not change from control in the early phase and did not subsequently increase, there was no late inotropic response. These data suggest that the Anrep effect in the awake dog is closely related to a recovery from subendocardial ischemia.