Effects of interaction between hemorrhagic hypotension and hypoxia on the renal circulation were examined in awake rabbits. The hypothesis tested was that renal vasoconstriction during hemorrhagic hypotension is affected by arterial PO2 [partial pressure of O2] (PaO2). Awake rabbits were placed into an environmental chamber and exposed to either normoxia (PaO2 > 100 mm Hg) or hypoxia (PaO2 .ltoreq. 40 mm Hg). Renal blood flow (RBF) was measured with 15 .mu.m microspheres during normotension (mean arterial pressure = 86-97 mm Hg), moderate hemorrhagic hypotension (mean arterial pressure = 62-65 mm Hg), and severe hemorrhagic hypotension (mean arterial pressure = 49-50 mm Hg). During normotension, RBF was 461 .+-. 46 and 330 .+-. 30 ml/min per 100 g (mean .+-. SEM [standard error of the mean]) in the normoxic and hypoxic groups, respectively (P < 0.05), and renal vascular resistance (RVR) was 0.21 .+-. 0.03 and 0.31 .+-. 0.04 mm Hg per ml/min per 100 g in the normoxic and hypoxic groups, respectively (NS [not significant]). Renal blood flow fell progressively in each group during hypotension, but the magnitude of this response was unaffected by the level of PaO2. In contrast, RVR during severe hypotension was 0.42 .+-. 0.11 and 2.08 .+-. 0.57 mm Hg per 100 g for normoxia and hypoxia, respectively (P < 0.05), and the increase in RVR during severe hypotension compared to normotension was greater in the hypoxic than normoxic group (P < 0.05). In unanesthetized rabbits, hypoxia reduces RBF but does not change RVR significantly during normotension, and hypoxia potentiates the increase in RVR during hemorrhagic hypotension.