Oxygen tension within the renal parenchyma is influenced by two factors: metabolic demand and oxygen supply. There are three regions within the kidney in which there is an anatomical basis for limited oxygen availability. The first is the inner stripe where oxygen dfision between arterial and venous vasa recta reduces PO,. The other two are the outer stripe and medullary rays which are fed by 02-poor blood from venous vasa recta. The balance between oxygen demand and supply is most critical in the inner stripe where the po2 is most influenced by transport activity. In contrasr, altering transport activities in the outer stripe will not change the prevalence of hypmic S3 injury but will alter its type (i.e., cell fragmentation related to high GFR and increased workload versus cell edema related to low GFR and minimal workload). The effect of transport activity on medullary ray PO2, has not been well defined. Using sensitive oxygen microelectrodes, cortical PO2, (52±2 mm Hg) in the rat was found to be higher than medullary PO2 (21±2 mm Hg, P<0.001). How are these observations reflected in current models of acute renal failure? The ischemia-reflow model affects proximal tubules with a predilection for S3 (located within the outer stripe of medulla) afier short-term ischemia. With hyperfiltration (induced by glycine or renal hypertrophy) and the pursuant increase in transport related 02 demand, hypmic mTAL inner stripe injury becomes prominent. Renal parenchymal hypertrophy exaggerates injury in the contrast nephropathy model, in which mTAL inner stripe injury is a predominant feature and medullary PO, is very low. In this model, with the additional stimulus of hyperjlltration induced by amino acid infusion, metabolic 02 demand rises and the mTAL inner stripe injury markedly increases. Myoglobin-induced renal failure is another example of hypoxia-related renal injury, but other factors may be important as well. Thus, alterations in the balance between oxygen supply and demand in certain regions of the kidney may be crucial in the pathogenesis of various models of acute renal failure.