The present study tested the hypothesis that, during acute bleeding, the development of tissue hypoxia might be reflected by an abrupt widening in arteriovenous gradient for PCO2 (AV PCO2) and for pH (AV pH) as accurately as by an increase in blood lactate levels. Twenty-four anesthetized (isoflurane 1.4% end-tidal), paralyzed, and mechanically ventilated dogs submitted to progressive hemorrhage were studied. Oxygen uptake (VO2) was derived from expired gas analysis and oxygen delivery (DO2) was calculated by the product of the thermodilution cardiac index and the arterial O2 content. During the first part of the protocol, VO2 remained stable as the progressive reduction in DO2 was associated with a corresponding increase in O2 extraction (O2ER). Blood lactate increased slightly but not significantly. AV PCO2 and AV pH increased significantly, essentially related to venous respiratory acidosis. The critical value of DO2 below which VO2 decreased was 8.95 +/- 1.60 mL.min-1.kg-1. Below this value, there was a marked increase in blood lactate and an abrupt widening in AV PCO2 and AV pH gradients. The critical value of DO2 obtained from blood lactate, AV PCO2 and AV pH were similar to those obtained from VO2 (8.60 +/- 1.12; 8.73 +/- 1.40; 8.78 +/- 1.37, respectively; P = not significant). A significant correlation was found, during the hemorrhage protocol, between blood lactate and AV PCO2 (r = 0.84; P < 0.001) or AV pH (r = 0.78; P < 0.001). Therefore, AV PCO2 and AV pH represent simple but reliable indicators of tissue hypoxia during hemorrhagic shock.