To examine the mechanism of the increase in cerebral blood flow induced by L-arginine administration after traumatic brain injury, the cerebral hemodynamic effects of L-arginine, D-arginine, and the free radical scavengers superoxide dismutase (SOD) and catalase were compared in the controlled cortical impact injury model in rats. Animals were anesthetized with isoflurane. Measured parameters included mean blood pressure, intracranial pressure, cerebral blood flow using laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations using an NO electrode. L-arginine, but not D-arginine, administration resulted in a significant increase in tissue NO concentrations and an improvement in LDF at the impact site, compared to control animals given saline. Administration of SOD alone and in combination with catalase resulted in a significant increase in brain tissue NO concentrations. However, LDF was consistently improved only when both SOD and catalase were given. These studies support the theory that L-arginine administration improves post-traumatic cerebral blood flow by increasing NO production. Free radical production after trauma may also contribute to the reduction in CBF by inactivating NO.