The influence of an early chronic phenobarbital treatment on cerebral arteriovenous differences of glucose, lactate, pyruvate, ß-hydroxybutyrate and acetoacetate was studied in suckling rats. The animals were treated from day 2 to 21 after birth by a daily injection of 50 mg/kg phenobarbital or by saline and were studied at 10, 14 and 21 days. Phenobarbital treatment induced a decrease in cerebral arteriovenous difference of glucose at P14 and no change at P10 and P21. The barbiturate did not have any influence on cerebral arteriovenous difference of lactate and pyruvate at the three stages studied. Cerebral uptake of ß-hydroxybutyrate was unchanged at P10 and increased by two-fold at P14 and by threefold at P21 by phenobarbital. Cerebral arteriovenous difference of acetoacetate was low and did not change with the pharmacological treatment. At P14 and P21, the calculated amount of oxygen used by the brain for the oxidation of ketone bodies was twice as high in barbiturate- as in saline-treated rats and reached values of 47 and 16% respectively in phenobarbital-exposed animals. In addition, the barbiturate seemed to affect the carrier process of ß-hydroxybutyrate from blood to brain. The results of the present study are in good agreement with previous data from our laboratory showing that an early chronic phenobarbital treatment is able to induce a shift in the cerebral energy metabolism balance in favor of ketone bodies.