The authors determined the effect of propofol on cerebral blood flow, intracranial pressure, and cerebral arteriovenous oxygen content difference in severely brain-injured patients during orthopedic treatment of fractures of the extremities. The Glasgow Coma Scale score was 6 or 7 at the time of the study. Data were collected in the operating room before and during (5 and 15 min) administration of propofol (2 mg/kg iv bolus immediately followed by a 150 μg · kg−1· min−1infusion) before surgical stimulation. Propofol was infused during 41.4 ± 7.3 min. After operation, the last set of measurements was made 15 min after propofol was stopped. The study was performed on 10 adults (age range, 15–40 yr) whose lungs were mechanically ventilated (air/O2) and who were sedated (phenoperidine, 1 mg/h), and was conducted using a radial artery cannula; a 7.5-Fr, thermodilution, flow-directed, pulmonary artery catheter; an intraventricular catheter; and a catheter in the jugular venous bulb. The133xenon intra-internal carotid artery injection technique was used to determine regional cerebral blood flow (rCBF). Anesthetic blood concentration of propofol (3–5 μg/ml) was associated with decreases in cerebral perfusion pressure (CPP; from 82 ± 14 to 59 ± 7 mmHg;P< 0.001), rCBF (from 35 ± 6 to 26 ± 5 ml · 100 g−1· min−1;P< 0.01), and intracranial pressure (ICP; from 11.3 ± 2.6 to 9.2 ± 2.5 mmHg;P< 0.001). Cerebrovascular resistance and cerebral arteriovenous oxygen content difference were unchanged. After propofol was stopped (at a blood propofol concentration theoretically corresponding to recovery from anesthesia), rCBF and ICP returned to preinduction values without any rebound. It was concluded that propofol reduces ICP but may lower CPP because of its effects on mean arterial pressure. Propofol appears to exert no consistent effect on cerebral vascular resistance and does not alter cerebral arteriovenous oxygen content difference.