Impairment of systolic coronary blood flow (CBF) may be mediated by intramyocardial pressure (PIM). However, the effect of systole on the magnitude and transmural distribution of coronary blood flow has not been investigated. The purpose of this study was to measure this effect, and, indirectly, intramyocardial pressure. It is assumed that intramyocardial pressure acts on the coronary vessels as a Starling resistor, such that local coronary blood flow is determined by the equation: Coronary perfusion pressure minus intramyocardial pressure equals resistance times coronary blood flow. This equation was integrated with respect to time and solved simultaneously for intramyocardial pressure and resistance by measuring regional coronary blood flow (radioactive microsphere technique) during maximal coronary vasodilatation in two states: beating and hypocalcemic diastolic arrest. Measurements were made in 7 to 16 concentric layers of the left ventricle of 16 dogs. Intramyocardial pressure ranged from near zero to twice peak left ventricular pressure. The transmural distribution of intramyocardial pressure and systolic coronary blood flow depended on preload. The transmural distribution of the ratio of intramyocardial pressure to coronary perfusion pressure was not significantly different from unity across the left ventricular wall at low levels of preload (0 to 4 mm Hg). At moderate to high levels of preload (7 to 35 mm Hg) this ratio was not different from unity (mean 1.03 and 0.96) in the two inner fifths of the left ventricular wall, but was significantly lower (mean 0.79, 0.64 and 0.41, respectively) in the middle and two outer fifths. These data show that intramyocardial pressure shuts off systolic coronary blood flow across the entire left ventricular wall at low levels of preload, and at high levels of preload determines a gradient of decreasing systolic coronary blood flow from the subepicardium to zero in the subendocardial layers. This finding suggests that a dilated or failing left ventricle receives systolic flow to the outer myocardial layers, whereas at low preload levels myocardial perfusion occurs entirely during diastole.