Global cerebral oxygenation, perfusion pressure, and expired CO2 tension were continuously monitored in 69 adults with acute severe closed brain trauma. Cerebral oxygenation was assessed by continuous fiberoptic monitoring of jugular bulb oxyhemoglobin saturation, in conjunction with continuous monitoring of arterial oxyhemoglobin saturation. Jugular desaturation associated with arterial desaturation (hypoxemic cerebral hypoxia) was evaluated and managed. A total of 121 episodes of combined arterial and jugular desaturation were documented, 76 in the presence of gross abnormalities identified on chest roentgenograms. Prolonged episodes that did not respond promptly to treatment occurred 32 times in 12 patients, usually after the initial 72 hours posttrauma. The remaining 89 episodes promptly responded to treatment and occurred predominantly within the initial 72 hours. Profound but brief desaturation was not associated with neurological deterioration, while profound and prolonged desaturation was accompanied by significant decreases in Glasgow Coma Scale scores, even though intracranial pressure levels were not significantly different in these two groups. Global cerebral hypoxia that does not respond promptly to treatment appears to be independently deleterious to neurological function in severely head-injured patients.