A previous study indicated that the mortality rate after severe head injury (Glasgow coma score less than or equal to 7) was higher on each of the first 2 days after injury (early deaths) than on any subsequent day (late deaths). The low Glasgow coma scores, high incidence of unreactive pupils, and refractoriness to treatment of patients dying within 48 hours of injury suggested that many such patients had sustained irreversible brain injury. To determine the extent to which events at impact sealed the fate of those dying early deaths after head injury, we compared the pathology of cases of early and late death. Of 2000 patients with head injury admitted to the neurosurgery service during a 6-year period, there were 138 deaths and 56 autopsies. Seventy-two per cent of the patients who died during the first 48 hours after injury had widespread homogenizing necrosis of neuron or direct brain stem injury, considered to represent irreversible brain damage. Only 19% of those dying later deaths had these pathological changes. Patients with severe homogenizing necrosis or direct brain stem damage were usually injured in high speed motor vehicle accidents and had low Glasgow coma scores and unreactive pupils on admission to the hospital. They usually did not have hematomas, but had brain swelling and herniations. Patients dying without homogenizing necrosis or direct brain stem injury usually were injured by blows or falls, usually had hematomas, and less often had unreactive pupils and low Glasgow coma scores on admission. The findings suggest that there is a significant irreducible mortality rate after head injury incurred in high speed motor vehicle accidents. Recognition of such cases is important in the comparison of series and in the evaluation of treatment for head injury.