In neonates suffering hypotensive or asphyxial episodes, the brain stem is particularly vulnerable to selective neuronal necrosis. Typically, the pattern is one of generalized neuronal necrosis within well-defined brain stem cranial nerve nuclei, or random neuronal degeneration within the reticular formation. More recently, isolated cases of severe partial or total cystic necrosis of the brain stem reticular formation have been recorded. The pathogenesis is poorly understood at this time, but may be similar to the less severe (but more often recognized) nuclear or focal neuronal loss. Three infants are presented in which severe necrosis of the brain stem occurred. In each, the clinical setting was one of sudden and abrupt worsening of the patient's cardiovascular status.