SummaryNewborn humans may develop myocardial dysfunction in conjunction with severe birth asphyxia. Subendocardial or papillary muscle ischemia appears to be the basis for the myocardial dysfunction, yet patent coronary arteries have been demonstrated in the nonsurvivors. The asphyxiated newborns also have experienced hypoxemia, which has been suggested as the cause of myocardial ischemia. This study was designed to determine the relationship between reduced aortic blood oxygen content and blood flow as well as oxygen delivery within different regions of the heart. Three days after surgery, we measured blood flow and oxygen delivery to the free walls and papillary muscles of the right and left ventricles, the ventricular septum, and the atria in 10 lambs, during 20-min periods in 8-10% and 5-6% environmental oxygen concentrations. In each region of myocardium, blood flow increased linearly as the aortic blood oxygen content decreased. The slopes of the regression lines were similar for each region of ventricular myocardium. Atrial myocardial blood flow also increased as a linear function of the reductions in aortic blood oxygen content, but at a slower rate than in the ventricular regions. Hypoxemia was associated with increased oxygen delivery in each region of myocardium, but the two variables were not related in a linear or quadratic fashion. The results demonstrate that isolated hypoxemia is associated with increased blood flow and oxygen delivery in the free walls and papillary muscles of the right and left ventricles, the ventricular septum, and the atria.