Previous studies have suggested a link between renal metabolism and local kidney hemodynamics to prevent potential hypoxic injury of particularly vulnerable nephron segments, such as the outer medullary region. The present study used three different inspiratory oxygen concentrations to modify renal metabolic state in the conscious rat (hypoxia 10% O2, normoxia 20% 02, and hyperoxia 100% 02). Renal blood flow (RBF) was assessed by ultrasound transit time; renal perfusion pressure (RPP) was controlled by a hydroelectric servo-control device. Local RBF was estimated by laser-Doppler flux for the cortical and outer medullary region (2 and 4 mm below renal surface, respectively). Hypoxia led to a generalized significant increase in RBF, whereas hyperoxia-induced changes did not (hypoxia 6.6 +/- 0.6 ml/min versus normoxia 5.7 +/- 0.7 ml/min, P < 0.05). Moreover, regional and total RBF autoregulation was markedly attenuated by hypoxia. Conversely, hyperoxia enhanced RBF autoregulation. Under normoxic and hyperoxic conditions, medullary RBF was very well maintained, even at low RPP (medullary RBF: approximately 70% of control at 50 mmHg). The hypoxic challenge, however, significantly diminished the capacity to maintain medullary blood flow at low RPP (medullary RBF: approximately 30% of control at 50 mmHg, P < 0.05). These data suggest that renal metabolism and renal hemodynamics are closely intertwined. In response to acute hypoperfusion, the kidney succeeds in maintaining remarkably high medullary blood flow. This is not accomplished, however, when a concomitant hypoxic challenge is superimposed on RPP reduction.