A protein-free diet causes a paradoxical increase of blood ammonia levels that seems to be due to decreased liver content of acetylglutamate, the physiological activator of carbamylphosphate synthetase. The purpose of this study was to assess whether oral administration to rats of carbamylglutamate, a metabolically stable activator of carbamylphosphate synthetase, could decrease the blood ammonia levels increased by the protein-free diet. We show that ingestion of moderate doses of carbamylglutamate increased about sixfold the liver content of carbamylphosphate synthetase activators and restores to normal values the blood ammonia levels. Excess ammonia is eliminated in urine as urea. These results indicate that carbamylglutamate, which is not toxic, could be useful in the treatment of hyperammonemia, especially in cirrhosis. (Hepatology 1991;15:446–448).