Moderate systemic hypothermia has been shown to improve neurologic outcomes in both fluid-percussion and cortical contusion models of experimental brain injury. Based upon initial clinical work, it was concluded that at temperatures < 32 degrees C, patients with severe brain injury were at increased risk of ventricular arrhythmias, and that rapid rewarming immediately postinjury predisposed to intracranial pressure increases. Subsequent clinical studies of moderate hypothermia (32 degrees C) for 24- to 48-hr duration with slow rewarming in human brain injury showed indications of neurologic improvement and a low incidence of hypothermia-related complications. Based upon the strengths of both laboratory and clinical data, a multicenter (nine centers), randomized, prospective trial testing moderate systemic hypothermia in patients with severe brain injury has been organized. This trial, funded by National Institutes of Health, National Institute of Neurological Disorders and Stroke, began on October 20, 1994. Five hundred patients are to be treated in an intent-to-treat protocol using standard management at normothermia versus standard management at hypothermia. The trial is designed to detect an absolute shift of 12% in the percentage of patients achieving satisfactory outcome (good recovery/moderate disability) at a power of 85% at 6 months postinjury. The efficacy of hyperbaric oxygen administered every 8 hrs for 1-hr duration for a 2-wk period has also been tested in patients after severe brain injury. While the mortality rate was reduced in the treated group, the percentage of favorable outcomes was unchanged. Further studies are in progress.