The influence of phenobarbital (PhB) on the utilization of ß-hydroxybutyrate by the cerebral cortex and the cerebellum was studied in rats during postnatal maturation. The animals were treated from day 2 to day 35 after birth either by a daily injection of 50 mg/kg PhB or by saline. The rats were studied at 5 postnatal stages: 7, 10, 14, 21 and 35 days. Plasma ß-hydroxybutyrate and acetoacetate levels reached their peak values between 10 and 14 days after birth. The concentration of both ketone bodies was significantly higher in PhB- than in saline-treated rats between 10 and 35 days after birth. The total incorporation of [3-14C]ß-hydroxybutyrate into amino acids reached a peak value at 14 days after birth and was down to very low values at 35 days. It was higher in PhB- than in saline-treated rats. The specific radioactivity values of glutamate, glutamine, aspartate and GABA were significantly higher in PhB- than in saline-treated especially at 10 days after birth. These results demonstrate that a PhB treatment induces an increase in brain ketone body utilization in neonate rats, which is likely to balance the decrease in brain glucose utilization induced by this pharmacological treatment.