The brain acid-base status and metabolites were measured in 17 mongrel dogs that were anesthetized with pentobartital (20-25 mg/kg initially and 2-4 mg/kg every 2 h thereafer), or initially anesthetized with sodium pentothal (20 mg/kg) and placed on nitrous oxide (70% N2O-30% 02) for 5-51/2 h under normoxic, normocapnic conditions. In comparison with the awake, unrestrained state, both anesthetics caused a significant metabolic acidosis in both plasma and cisternal CSF. No significant differences between anesthetics were found with: (1) acid-base status in plasma or brain ECF and ICF; (2) cerebral tissue energy charge potential; or (3) creatine and phosphocreatine levels and the creatine to phosphocreatine ratios. No differences were found in the ATP to ADP ratios, but lactate to pyruvate ratios were significantly lower. Within pentobarbital anesthesia, citrate levels were higher, while other TCA metabolites measured were lower. Further, the citrate to alpha-ketoglutarate and malate to oxaloacetate ratios were significantly increased. We propose that pentobarbital anesthesia lowers metabolic activity in brain tissue and the primary site of 'crossover' inhibition is between citrate and alpha-ketoglutarate.