Although the presence of an isoelectric electroencephalogram (EEG) in an older patient may reflect brain death caused by an acute brain injury, this electrographic abnormality may appear in more diverse clinical situations in the neonate with encephalopathy. During a 6-year period, 20 neonates were identified with a severe encephalopathy on neurologic examination who had at least one isoelectric EEG during their treatment in a neonatal intensive care unit. Seventy-four EEG recordings were obtained including 36 isoelectric EEG records. Partially preserved clinical brain function was present in 15 (75%) of 20 infants at the time an isoelectric EEG was obtained. The initial EEG was isoelectric in 16 of 20 infants. Although electrographic activity reemerged in nine of these infants, significant clinical improvement was seen in only two patients. Thirteen of 20 neonates also had electrographic or other evidence of clinical seizures. Of the five survivors (25%), three had severe neurologic sequelae. The remaining two had either transient or persistent neurologic deficits. An isoelectric EEG may be obtained in the neonate with partially preserved brain function and, therefore, may not be a reliable confirmatory test of neonatal brain death. In addition, serial EEGs not only can help assess the severity of a neonatal encephalopathy but also may correlate with chronic and acute neurologic insults.