Branched-chain amino acids (BCAA) are known to improve hepatic encephalopathy as well as protein malnutrition in cirrhosis. However, such effects in acute hepatic failure (AHF) remain to be elucidated. The current study was conducted to investigate whether BCAA improves protein metabolism in AHF. AHF was induced in male Donryu rats weighing approximately 230 g by giving 60 mgkg lipopolysaccaride intravenously and 800 mgkg D-galactosamine hydrochloride intraperitoneally. From 18 hours after injection, AHF rats and control rats were given one of the following five solutions intravenously for 6 hours: 1) saline, 2) lWo glucose, 3) standard 10% amino acid formula with total nitrogen content of 12.2 g/L and BCMaromatic amino acid molar ratio of 37.05, 4) BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 148.2, or 5) an active placebo against BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 37.05. In parallel, each group was given a continuous idksion of W-leucine. After the plasma radioactivity of 14C-leucine and the expired 14C02 level reached a plateau, protein turnover was analyzed according to the kinetic model proposed previously by Waterlow. When compared with the control, rates of total protein turnover (total flux), oxidation, and breakdown all increased significantly in AHF. Infusion of standard 10% amino acid formula, BCAA-enriched solution or the placebo in AHF increased total flux and oxidation significantly as compared with the effect of saline or 10% glucose. Although saline, 10% glucose, standard 10% amino acid formula, and the placebo had no effect on synthesis rate, it was increased significantly with BCAA-enriched solution. Breakdown was not suppressed with any solution. These results suggest that rats with AHF are in a catabolic state and that any of the three amino acid solutions can be oxidized to provide energy in AHF. In addition, infusion of BCAA-enriched solution may have a specific protein-sparing ef-Abbreviations: BCAA, branched-chain amino acids; AAA, aromatic amino acids; AHF, acute hepatic failure; FHF, fulminant hepatic failure.