Verification of the current view that subendocardial preponderance of ischemia is due to greater forces generated in the deep myocardial layer during systole was undertaken. In anesthetized mongrel dogs transient ischemia was produced in two different situations of altered systolic forces. First, in order to remove that part of the systolic force which is related to intracavitary pressure, left ventricular bypass was created and the left ventricle vented. Second, in order to even out the transmural distribution of the remaining part of the forces, which is due directly to distortion and displacement of contracting fibers, ventricular fibrillation was induced in addition to venting under conditions of total cardiopulmonary bypass. In both series of experiments the ischemic area was then reperfused, normal circulation re-established and the animal allowed to survive for 3-5 days. After sacrifice, ischemic necrosis was found almost exclusively in the subendocardium. The persistence of subendocardial preponderance of ischemia under conditions of left ventricular venting and absence of coordinated contraction shows that uneven distribution of intramural forces generated during systole is not the primary cause of this preponderance.