In vivo phosphorus 31 nuclear magnetic resonance (31P NMR) spectroscopy was used to evaluate changes in cerebral high-energy phosphate compounds in 8 infants with seizures. During the study 4 babies had seizures that caused a 50% decrease in the phosphocreatine to inorganic phosphate (PCr/Pi) ratio. Focal seizures caused lateralized decreases in the PCr/Pi ratio; generalized seizures caused bilateral decreases. Postictal spectra had increased PCr/Pi ratios, presumably due to postictal inhibition. Interictal 31P NMR spectra were normal. One patient's seizures were successfully treated with intravenously administered phenobarbital during NMR data acquisition, causing an immediate increase in the PCr/Pi ratio from 0.7 to 1.2. These studies indicate that cerebral PCr concentration decreases by approximately 33% and that oxidative metabolism increases by approximately 45% during neonatal seizures. Five babies had PCr/Pi ratios of less than 0.8 during seizures and subsequently developed long-term neurological sequelae, which suggests that neonatal seizures may cause or exacerbate cerebral injury by increasing cerebral metabolic demands above energy supply.