Abstract: Acute hepatic failure is associated with many biochemical abnormalities in plasma and brain. Changes that correlate well with the degree of behavioral impairment may be important factors in the development of encephalopathy. We measured the concentrations of intermediary metabolites, ammonia, and amino acids in brain and plasma and the rate of whole-brain glucose utilization in rats with an acutely devascularized liver. In all rats an estimate of the grade of encephalopathy (reflected by behavioral impairment) was made. Rats underwent portacaval shunting and hepatic artery ligation (or sham operation) and were kept normoglycemic and normothermic thereafter. We sampled blood and whole brain (by near-instantaneous freeze-blowing) 2, 4, or 6 h later. There were no alterations in levels of high-energy phosphate metabolites in the brain or in metabolites associated with the glycolytic pathway and Krebs cycle, except lactate and pyruvate. Brain glucose use was decreased similarly at all times after surgery. Levels of ammonia and many amino acids were increased in brain and plasma; brain aspartate, glutamate, and arginine levels were decreased. The increases in content of plasma ammonia and brain glutamine, proline, alanine, and aromatic amino acids and the decreases in brain aspartate and glutamate were most strongly correlated with behavioral impairment.