Renal blood flow (RBF) can be reduced in rats and rabbits by up to 40% without significant changes in renal tissue PO₂. We determined whether this occurs because renal oxygen consumption changes with RBF, or due to some other mechanism. The relationships between RBF and renal cortical and medullary tissue PO₂ and renal oxygen metabolism were determined, in the denervated kidneys of anesthetized rabbits under hypoxic, normoxic and hyperoxic conditions. During artificial ventilation with 21% oxygen (normoxia), RBF increased 32±8% during renal arterial infusion of acetylcholine and reduced 31±5% during angiotensin II infusion. Neither infusion significantly altered arterial pressure, tissue PO₂ in the renal cortex or medulla, nor renal oxygen consumption. However, fractional oxygen extraction fell as RBF increased and the ratio of oxygen consumption to sodium reabsorption increased during angiotensin II infusion. Ventilation with 10% oxygen (hypoxia) significantly reduced both cortical and medullary PO₂ (60-70%), while ventilation with 50% and 100% oxygen (hyperoxia) increased cortical and medullary PO₂ (by 62-298% and 30-56% respectively). However, responses to altered RBF under hypoxic and hyperoxic conditions were similar to those under normoxic conditions. Thus, renal tissue PO₂ was relatively independent of RBF within a physiological range (±30%). This was not due to RBF-dependent changes in renal oxygen consumption. The observation that fractional extraction of oxygen fell with increased RBF, yet renal parenchymal PO₂ remained unchanged, supports the hypothesis that preglomerular diffusional shunting of oxygen from arteries to veins increases with increasing RBF, and so contributes to dynamic regulation of intrarenal oxygenation'.