Right ventricular failure has been noted in up to 25% of patients requiring a left ventricular assist device. Altered septal motion or function is one proposed mechanism of right ventricular failure during left heart bypass. We studied the effect of regional ischemia and reperfusion of the interventricular septum on right ventricular function during complete left heart bypass. In six calves the septal perforating branches of the proximal left anterior descending coronary artery were isolated for intermittent occlusion. Complete left heart bypass was established with a Pierce-Donachy left ventricular assist device. Right and left ventricular function were studied with two-dimensional echocardiography and with intraventricular pressure monitors. Establishment of left heart bypass did not significantly affect right ventricular developed pressure, right ventricular end-diastolic area, or right ventricular fractional change in area. Left heart bypass significantly (p less than 0.001) decreased percent systolic septal wall thickening. Septal ischemia during left heart bypass resulted in a decrease in right ventricular developed pressure (p = 0.09), significant increase in right ventricular end-diastolic area (p = 0.002) and significant decrease in right ventricular fractional change in area (p less than 0.001), and a further decrease in interventricular septal wall thickening (p = 0.016). The interventricular septum became thin with flattening of its normal contour. Septal reperfusion resulted in right ventricular recovery with significant improvement in all factors (p less than 0.02). Similar results were documented during a second episode of septal ischemia with recovery after septal reperfusion. In some cases, septal ischemia may be an important factor in the development of right ventricular failure during left heart bypass.