OBJECTIVE Hypertonic saline is emerging as a potentially effective single osmotic agent for control of acute elevations in intracranial pressure (ICP) caused by severe traumatic brain injury. This study examines its effect on ICP, cerebral perfusion pressure (CPP), and brain tissue oxygen tension (PbtO2). METHODS Twenty-five consecutive patients with severe traumatic brain injury who were treated with 23.4% NaCl for elevated ICP were evaluated. Bolt catheter probes were placed in the noninjured hemisphere, and hourly ICP, mean arterial pressure, CPP, and PbtO2 values were recorded. Thirty milliliters of 23.4% NaCl was infused over 15 minutes for intracranial hypertension, defined as ICP greater than 20 mm Hg. Twenty-one male patients and 4 female patients aged 16 to 64 years were included. The mean presenting Glasgow Coma Scale score was 5.7. RESULTS Mean pretreatment values included an ICP level of 25.9 mm Hg and a PbtO2 value of 32 mm Hg. The posttreatment ICP level was decreased by a mean of 8.3 mm Hg (P < 0.0001), and there was an improvement in PbtO2 of 3.1 mm Hg (P < 0.01). ICP of more than 31 mm Hg decreased by 14.2 mm Hg. Pretreatment CPP values of less than 70 mm Hg increased by a mean of 6 mm Hg (P < 0.0001). No complications occurred from this treatment, with the exception of electrolyte and chemistry abnormalities. At 6 months postinjury, the mortality rate was 28%, with 48% of patients achieving a favorable outcome by the dichotomized Glasgow Outcome Scale. CONCLUSIONS Hypertonic saline as a single osmotic agent decreased ICP while improving CPP and PbtO2 in patients with severe traumatic brain injury. Patients with higher baseline ICP and lower CPP levels responded to hypertonic saline more significantly.