Background: Direct measurement of brain tissue oxygen (PbrO 2) via polarographic micro-electrodes is being utilized as a new monitoring tool in severe head injury and other neurologic critical illnesses. While this may provide unique information about cerebral metabolism and other physiologic parameters in the injured brain, the relationship between P brO2 and end-tidal (ETCO2) or mean arterial pressure (MAP) in the normal brain is not known. Methods: Licox Clark-type oxygen probes were inserted in the frontal white matter of 12 swine. General anesthesia was maintained with isoflurane, fentanyl, and pancuronium with a baseline FiO2= 1.0. In 7 animals, alterations in ETCO2 (range 13-72 mmHg) were induced via hyperventilation or instillation of CO 2 into the breathing circuit. In 7 animals, MAP (range 33-200 mmHg) was altered pharmacologically (using phenylephrine for hypertension or a combination of nitroprusside and esmolol for hypotension) or by systemic hemorrhage. Cerebral blood flow (CBF) was measured in 3 animals using a novel intraparenchymal thermal-diffusion probe (n=2) or a laser doppler flow probe (n=1). Results: Mean baseline PbrO2 was 41.9±11.3 mmHg. PbrO2 varied linearly with changes in ETCO 2 over a range from 20-60 mmHg, (r2=0.6971). Within this linear range, PbrO2 changed an average of 1.4 mmHg (3% of baseline) per mmHg change in ETCO2. Minimum PbrO 2 with hypocarbia was 5.9 mmHg and maximum with hypercarbia was 132.4 mmHg. PbrO2 varied with MAP in a sigmoid fashion suggestive of autoregulation between a MAP of 70-150 mmHg (r2=0.7235) . Minimum PbrO2 with hypotension was 1.4 mmHg and maximum with hypertension was 97.2 mmHg. CBF also correlated linearly with ETCO 2 (r2=0.9329) and in a sigmoid manner with MAP (r 2=0.8152). Conclusions: In the uninjured brain, PbrO 2 exhibits CO2 reactivity and pressure autoregulation. The relationship of PbrO2 to ETCO2 and MAP appear similar to those for CBF with ETCO2 and MAP as measured here and historically established. This suggests that under normal conditions, P brO2 is more likely a reflection of CBF than an independent measure of cerebral oxygen metabolism.