Hyperammonemia is a feature of acute liver failure (ALF), which is associated with increased intracranial pressure (ICP) and brain herniation. We hypothesized that a combination of L-ornithine and phenylacetate (OP) would synergistically reduce toxic levels of ammonia by (1) L-ornithine increasing glutamine production (ammonia removal) through muscle glutamine synthetase and (2) I n patients with acute liver failure (ALF) increased intracranial pressure (ICP) leads to brain herniation, which accounts for 30% of deaths. 1 Liver failure results in hyperammonemia, which leads to toxic levels of ammonia in the brain. In patients with ALF, an arterial ammonia level of Ͼ150 mol/L has been shown to correlate with severity of intracranial hypertension 2 and deaths from brain herniation. 3 More recently, ammonia levels were shown to be predictive of increased ICP 4 and changes in blood ammonia concentration determined death due to cerebral edema in patients with ALF. 5Abbreviations: ALF, acute liver failure; GS, glutamine synthetase; HE, hepatic encephalopathy; ICP, intracranial pressure; OP, L-ornithine phenylacetate. From the