We describe our results on the effect in rats of two commonly used, volatile anesthetics on cerebral tissue PO2 (PtO2) and other physiological parameters at FiO2 levels ranging from 0.35 to 0.1. The study was performed in 12 rats that had lithium phthalocyanine (LiPc) crystals implanted in the left cerebral cortex. FiO2 was maintained at 0.35 during surgical manipulation and baseline EPR measurements, after which time, each animal was exposed to varying levels of FiO2 (0.26, 0.21, 0.15, and 0.10) for 30 minutes at each level. No significant difference in PtO2 was observed between the isoflurane and halothane groups at any FiO2 level, and the cerebral arterial PO2 (PaO2) also was similar for both groups. However, the cerebral PtO2 under both isoflurane and halothane anesthesia was lower during hypoxia (FiO2 < or = 0.15) than under normoxia (FiO2 = 0.21) and there was a significant difference in mean arterial blood pressure (MABP) between isoflurane and halothane groups under both mild and severe hypoxia. The pH and cerebral arterial PCO2 (PaCO2) were similar for the halothane and isoflurane groups during normoxia (FiO2 = 0.21) and mild hypoxia (FiO2 = 0,15), but following severe hypoxia (FiO2 = 0.10), both parameters were lower in the halothane anesthetized animals. These results confirm that cerebral PO2 cannot be inferred directly from measurements of other parameters, indicating that methodology incorporating continuous direct measurement of brain oxygen will lead to a better understanding of cerebral oxygenation under anesthesia and hypoxia.