A common pattern of hypoxic-ischemic cerebral injury in the term newborn involves predominantly cerebral cortex and subcortical white matter. We describe 20 term newborns with moderate or severe acute hypoxic-ischemic encephalopathy who exhibit a different pattern of abnormalities on computed tomography, with evidence of decreased tissue attenuation predominantly in thalami and basal ganglia and relative preservation of cerebral cortex and white matter. Profound, acute hypoxic-ischemic insult (eg, umbilical cord prolapse, uterine rupture, or massive placental abruption) was documented in 16 of 20 infants (80%). Characteristic clinical features during the newborn period included irritability, tonic posturing of limbs, and persistent lower cranial nerve dysfunction, often with prominent tongue fasciculations. This pattern of central injury appears to be highly predictive of poor outcome; 7 newborns (35%) died, and all survivors who had follow-up to 18 months of age (11) had major neurological sequelae (eg, spastic quadriplegia, choreoathetosis, and persistent feeding problems). This pattern of hypoxic-ischemic cerebral injury corresponds closely to experimental animal models of "acute total" perinatal asphyxia.