A multicenter double-blind randomized trial was conducted to examine the efficacy of a high dose of methylprednisolone (1,000-mg bolus and daily thereafter for ten days) compared with a standard dose (100-mg bolus and daily thereafter for ten days) in 330 patients with acute spinal cord injury. No difference in neurological recovery of motor function or pinprick and light touch sensation was observed between the two treatment groups six weeks and six months after injury. The lack of a treatment effect was independent of the severity of the initial lesion or the time from injury to starting treatment. Although not statistically significant, early case fatality was greater in the high-dose protocol (relative risk of 3.1 and 1.9, less than or equal to 14 and 15 to 28 days after injury, respectively) but not from 29 to 210 days after injury. Wound infections of both trauma and operative sites were more prevalent in the high-dose regimen (relative risk of 3.6).