Background: A cerebral oximeter measures oxygen saturation of brain tissue noninvasively by near infrared spectroscopy. The accuracy of a commercially available oximeter was tested in healthy volunteers by precisely controlling end-tidal oxygen (PETO2) and carbon dioxide (PETCO2) tensions to alter global cerebral oxygen saturation. Methods: In 30 healthy volunteers, dynamic end-tidal forcing was used to produce step changes in PETO2 resulting in arterial saturation ranging from similar to 70% to 100% under conditions of controlled normocapnia (each person's resting PETCO2) or hypercapnia (resting plus 7-10 mmHg). Blood arterial (SaO(2)) and jugular bulb venous (SjvO2) saturations during each PETO2 interval were determined by co-oximetry. The cerebral oximeter reading (rSO(2)) and an estimated jugular venous saturation ((S) over cap(jv)O(2)) derived from a combination of SaO(2) and rSO(2), were compared with the measured SjvO2. Results: The SjvO2 was significantly higher with hypercapnia than with normocapnia for the same SaO(2). The rSO(2) and (S) over cap(jv)O(2) were both highly correlated with SjvO2 for individual volunteers (mean r(2) = 0.91 for each relation); however, the slopes and intercepts varied widely among volunteers, in three of them, the cerebral oximeter substantially underestimated the measured SjvO2. Conclusions: During isocapnic hypoxia in healthy persons, cerebral oxygenation as estimated by near infrared spectroscopy precisely tracks changes in measured SjvO2 within individuals, but the relation exhibits a wide range of slopes and intercepts. Therefore the clinical utility of the device is limited to situations in which tracking trends in cerebral oxygenation would be acceptable.