Brain edema in hepatic encephalopathy has been associated with circulating ammonia that is metabolized to glutamine. We measured alterations in blood chemistry and brain regional specific gravity and ion and amino acid contents in models of simple hyperammonemia and liver failure induced by daily administrations of ammonium acetate (AAc) or thioacetamide (TAA), respectively. Serum and brain ammonia increased to similar levels (200 and 170% of control, respectively) in both experimental groups. Serum transaminase activities increased 10-fold in animals injected with TAA but were unchanged in animals given AAc injections. In both experimental groups glutamine was elevated in cerebral white matter, cerebral gray matter, and basal ganglia, whereas brain tissue specific gravity decreased in all brain regions, indicating edema formation. In the AAc group, we observed a decrease in glutamate and taurine contents concomitant with the development of brain edema. In these animals, cerebral gray matter specific gravity and taurine contents returned to control levels 24 h after the third AAc injection. TAA-injected animals demonstrated similar decreases in brain tissue specific gravity, whereas glutamine, glutamate, and taurine contents were all elevated. During hepatic encephalopathy, ammonia-induced changes in brain amino acid content may contribute to brain edema development.