In a prospective study of 32 cases of brain death, gross and microscopic pathological appearances of the CNS were statistically analyzed and correlated with EEG and clinical findings. The diagnosis of a "respirator brain" is best made grossly after fixation, using commonly known gross pathological criteria. The microscopic changes are more unpredictable and variable than the gross findings. Respirator brain changes that can be relied on to confirm the clinical-EEG diagnosis of brain death generally take about 12 hours to become manifest after electrocerebral silence (ECS) and/or cerebral circulatory arrest, and are unaffected by the time interval between termination of respiratory support and refrigeration of the body or by delays in performance of the autopsy. Loss of brain-stem reflexes, evidence of herniation, and deterioration of the EEG to ECS correlate significantly with the development of a respirator brain in the respirator-dependent, comatose patient.