The molar ratio of excitatory amino acid neurotransmitters (glutamate and aspartate) to inhibitory amino acid neurotransmitters (r-aminobutyric acid, GABA, and glycine) in the brain was diminished in acute hepatic failure rats with hyperammonemia, brain edema, and abnormal electroencephalograms. The ratio was further decreased with a marked elevation of arterial and brain ammonia levels 30 min after ammonium acetate was administered i.p. to hepatic failure rats. A continuous infusion of a branched chain amino acid (BCAA) solution before and after the ammonia loading effectively reversed the ammonia-induced lowering of this ratio; high ammonia contents in the brain were concomitantly decreased. Infusing glutamate instead of the BCAA solution failed to produce similar effects probably because of limited entry of glutamate into the brain. The above results suggest that excitatory and inhibitory amino acid neurotransmitter (glutamate, aspartate, and GABA) levels in the brain of hepatic failure rats might vary with abnormal cerebral ammonia metabolism.