The effects of an atypical barbiturate, valofan, and of a classical barbiturate, exobarbital, on the cerebral energy metabolism of rat have been evaluated under normoxic and hypobaric hypoxia conditions. In hypobaric hypoxia, the survival time was significantly increased by valofan 1.5 g/kg and exobarbital 0.05 g/kg in respect to the controls. In normoxia, valofan 1.5 g/kg (dose weakly sedative) significantly increased creatin-P level and reduced pyruvate and lactate concentrations; exobarbital 0.05 g/kg (anesthetic dose) showed a similar behavior except for glucose which was increased. In hypobaric hypoxia, valofan and exobarbital did not cause any change in the pool of labile phosphates, nor in the levels of pyruvate and lactate in respect to the controls. Repeated treatment (20 days) with the two drugs significantly altered the cerebral energy metabolism during normoxia conditions. The concentrations of ATP, creatin-P, glucose, pyruvate and lactate were increased, while L/P ratio was unaffected.