During flurothyl seizures in 4-day-old rats, cortical concentration of ATP, phosphocreatine and glucose fell while lactate rose. Cortical energy use rate more than doubled, while glycolytic rate increased fivefold. Calculation of the cerebral metabolic balance during sustained seizures suggests that energy balance could be maintained in hyperglycemic animals, and would decline slowly in normoglycemia, but would be compromised by concurrent hypoglycemia, hyperthermia or hypoxia. These results suggest that the metabolic challenge imposed on the brain by this model of experimental neonatal seizures is milder than that seen at older ages, but can become critical when associated with other types of metabolic stress.