The adequacy of cerebral tissue oxygenation (PtO(2)) is a central therapeutic end point in critically ill and anesthetized patients. Clinically, PtO(2) is currently measured indirectly, based on measurements of cerebrovascular oxygenation using near infrared spectroscopy and experimentally, using positron emission tomographic scanning. Recent developments in electron paramagnetic resonance (EPR) oximetry facilitate accurate, sensitive, and repeated measurements of PtO(2). EPR is similar to nuclear magnetic resonance but detects paramagnetic species. Because these species are not abundant in brain (or other tissues) in vivo, oxygen-responsive paramagnetic lithium phthalocyanine crystals implanted into the cerebral cortex are used for the measurement of oxygen. The line widths of the EPR spectra of these materials are linear functions of PtO(2). We used EPR oximetry in anesthetized rats to study the patterns of PtO(2) during exposure to various inhaled and injected general anesthetics and to varying levels of inspired oxygen. Rats anesthetized with 2.0 minimum alveolar anesthetic concentration isoflurane maintained the largest PtO(2) (38.0 +/- 4.5 mm Hg) and rats anesthetized with ketamine/xylazine had the smallest PtO(2) (3.5 +/- 0.3 mm Hg) at a fraction of inspired oxygen (FIO(2)) of 0.21, P < 0.05. The maximal PtO(2) achieved under ketamine/xylazine anesthesia with FIO(2) of 1.0 was 8.8 +/- 0.3 mm Hg, whereas PtO(2) measured during isoflurane anesthesia with FIO(2) of 1.0 was 56.3 +/- 1.7 mm Hg (P < 0.05). These data highlight the experimental utility of EPR in measuring PtO(2) during anesthesia and serve as a foundation for further study of PtO(2) in response to physiologic perturbations and therapeutic interventions directed at preventing cerebral ischemia. CONCLUSIONS Using in vivo electron paramagnetic resonance oximetry, we studied the patterns of cerebral tissue oxygenation (PtO(2)) during exposure to various inhaled and injected general anesthetics, and to varying levels of inspired oxygen. These data show that inhaled anesthetics result in larger levels of PtO(2) in the brain than do several injectable anesthetics. The results highlight the experimental utility of electron paramagnetic resonance in measuring PtO(2) during anesthesia and serve as a foundation for further study of PtO(2) in response to physiologic perturbations and therapeutic interventions directed at preventing cerebral ischemia.