The effect of the 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on neurologic outcome and cerebral edema was evaluated in adult male Sprague-Dawley rats subjected to a fluid percussion temporal brain injury followed by 45 min of hypoxia (PaO2 = 30.0 mm Hg). The rats were divided randomly into five groups. Bolus injections of a control drug or U74006F (1.0, 3.0, 10.0, or 30.0 mg/kg) were given 3 min and 3 h after the injury. Twenty-four hours after the injury, the neurologic status was evaluated, the rats were killed, and brain water content was determined by microgravimetry. U74006F did not significantly reduce brain water content at any dose level, nor did it affect rotorod walking or activity scores. However, rats treated with U74006F at a dose of 10.0 mg/kg had significantly better motor function scores (p < 0.05) than rats in the control group. These findings demonstrate the usefulness of U74006F as a cerebroprotective agent in this model of experimental head injury.