Little is known about the effect of post-traumatic mannitol infusion on cerebral metabolism and oxygenation. The purpose of this study was to investigate the effects of mannitol in comatose patients on PtiO2, PtiCO2 and brain tissue pH using Clark-type electrodes implanted into cerebral white matter. In the neurosurgical intensive care unit PtiO2, PtiCO2, brain tissue pH, arterial blood pressure, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and jugular bulb oxygen saturation (SjvO2) were prospectively studied in eleven patients with severe traumatic brain injury (TBI) during a total of 30 mannitol administrations (125 ml of 20% Mannitol infused over 30 min through a central vein). When the initial ICP before mannitol infusion was below 20 mmHg neither ICP nor any of the other parameters changed significantly during or after mannitol infusion. With a pre-infusion ICP above 20 mmHg a significant effect was seen on ICP (decrease from 23 +/- 1 to 16 +/- 2 mmHg at 60 min) and CPP (increase from 68 +/- 2 to 80 +/- 3 mmHg at 120 min). These effects were not reflected in PtiO2 or SjvO2, which were 29 +/- 4 mmHg and 61 +/- 3%, respectively, at the beginning of mannitol injection and remained unchanged during the observation period. PtiCO2 and brain tissue pH were not affected by mannitol infusion. Future studies should focus on the identification of ICP or CPP thresholds where infusion of mannitol may actually improve O2-supply to the brain.