Hemodynamic and electrocardiographic changes caused by acute ischemia of the interventricular septum (IVS) were studied in 33 anesthetized dogs. IVS ischemia was produced by occluding the first septal branch of the anterior descending coronary artery. Acute IVS ischemia resulted in a significant elevation of LVEDP in open-pericardium dogs in the absence of right ventricular pressure changes. With the pericardium closed, however, RVEDP rose substantially in addition to a further increase in LVEDP. Hemodynamic effects of the ischemia of the left ventricular free wall were larger than the changes caused by IVS dysfunction similar in size to the free wall ischemia. Twelove-lead electrocardiograms showed ST depression in the inferior leads, but neither ST elevation nor appearance of an abnormal Q wave was observed after the occlusion of the first septal coronary branch. A-V or intraventricular conduction disturbance was seen in one-third of the dogs. These data suggest that acute myocardial ischemia of the IVS affected only left ventricular function in the absence of the pericardium, while it affected the hemodynamics of both ventricules when the pericardium was intact. There were no ECG changes indicating interventricular ischemia except A-V or intraventricular conduction disturbances.