The multicenter, double-blind, randomized second National Acute Spinal Cord Injury Study (NASCIS 2) was conducted to assess the effectiveness of methylprednisolone in improving neurological function after acute spinal cord injury. At 6 weeks, patients treated within 8 hours of injury with methylprednisolone, given as an initial bolus of 30 mg/kg followed by infusion of 5.4 mg/kg/h over 23 hours, demonstrated significantly greater improvement in motor function and touch sensation than did those receiving either naloxone or placebo. Improvement in pinprick sensation was also greater in the methylprednisolone group. These differences were maintained at 6 months and 1 year after injury. The recovery of motor and sensory function in methylprednisolone-treated patients was found to be due primarily to reductions in the severity of the lesion in the spinal cord itself rather than to improvements in the level of injury or root function. A new trial, NASCIS 3, is evaluating a 48-hour course of methylprednisolone infusion as well as treatment with tirilazad mesylate, an inhibitor of lipid peroxidation without glucocorticoid activity.