Previous studies have shown that 1,3-butanediol (BD) had beneficial effects in various experimental models of hypoxia and ischemia but its mechanism of action remains unknown. BD is converted in the liver to ketone bodies and it has been proposed that preferential metabolism of ketone bodies rather than glucose as an energy substrate may reduced the deleterious accumulation of brain lactic acid during ischemia. However, the plasma acidosis induced by BD may limit its therapeutic use. Since BD is a racemic (DL-BD), its metabolic effect could be due to D(-) or L(+) isomer. The aim of the present study was to compare the effects of DL (25 or 50 mmol/Kg, i.p.), D (25 mmol/Kg, i.p.) and L-BD (25 mmol/Kg, i.p.) on 1) the physiological parameters and 2) the main Krebs cycle-associated intermediates in the rat brain. Citrate, alpha-categlutarate and malate levels were determined in cerebral cortex by enzymatic methods after freezing of the brain in situ in halothane anesthetized normoventilated rats.Blood pH decreased by 0.09 unit in rats given 25 mmol/Kg DL-BD and by 0.14 unit in rats given 50 mmol/Kg DL-BD or 25 mmol/Kg L-BD but it remained in the normal range in D-BD-treated rats. Both doses of DL-BD and D-BD induced a marked increase in plasma D-β-hydroxybutyrate (+742, +892 and +1883% respectively). On the other hand, L-BD treatment led to a slight increase (+183%) in plasma D-β-hydroxybutyrate but the high plasma acidosis associated to this treatment suggests that L-BD was oxidized to L-β-hydroxybutyrate which was not detected with our stereospecific enzymatic method. Citrate cortical level was increased by both doses of DL-BD (+9% and +14%) and D-BD (+10%) but remained unchanged after L-BD treatment. The increase in cortical citrate after DL-BD was not due to hyperketonemia since injection of DL-β-hydroxybutyrate (6 mmol/Kg), which mimicked the DL-BD induced hyperketonemia, had no effect on cerebral citrate level. It might be due to intracerebral conversion of DL-BD to ketone bodies. These results show the potential value of D-BD with regard to DL-BD. The D isomer, without lowering blood pH, has the same metabolic effect than the racemic, i.e. a supply of acetylCoA leading to an increase in citrate level.