Clinicopathological features were examined in 65 neonates and 8 stillborn infants with pontosubicular necrosis (PSN) compared to 57 neonates and 19 stillborn infants without PSN. Twelve out of 65 neonates with PSN had congenital heart disease and 3 out of 65 neonates showed persistent fetal circulation. On neuropathological examination, the frequency of neonates with PSN who also showed karyorrhetic/eosinophilic neurons in other regions of the brain stem, basal ganglia and thalamus was higher than in controls. The results of this study suggest that acute ischemia is an important underlying pathogenetic factor and PSN occurs in the prenatal as well as postnatal period.