In order to investigate metabolic derangements in hepatic failure brains, glucose utilization was studied in regard to glucose-derived amino acids. For this purpose, chronic hepatic failure models were produced in adult male Wistar rats by successive carbontetrachloride injection (0.20 ml/100 g, B. W., twice/week) for 13 weeks. They were confirmed to develop chemical changes compatible with hepatic failure, showing markedly elevated serum levels of NH3, GOT and ALP. Animals were killed by decapitation during fasting and the brains were removed immediately. After the parietal cortical slices were incubated with D-(U-14C) glucose for 15 min, they were homogenized in 75% ethanol and deproteinized with water saturated chloroform. And the radioactivities of liberated CO2 and glucose-derived amino acids (glutamate, glutamine, aspartate, alanine and GABA) obtained from the supernatants were measured. In chronic hepatic failure brains as compared to normal controls, the amount of radioactivity of the two major metabolites, namely glutamate and CO2, decreased (p less than 0.01), but that of aspartate and alanine changed insignificantly, while GABA formation increased (p less than 0.05) and glutamine synthesis tended to increase. The above results indicate not only that the overall glucose oxidation in chronic hepatic failure brains declines reflecting low production of glutamate and CO2, but also that glucose-derived glutamate is actively metabolized through GABA shunt and energy-consuming ammonia fixation.