Plasma and cerebrospinal fluid amino acid levels wee measured in 12 cirrhotic patients in grade 0 hepatic encephalopathy and 17 in grade 3-4 hepatic encephalopathy. In 5 of these patients amino acid determinations were performed during the evolution of the encephalopathy. No correlation was found between the degree of hepatic encephalopathy and the plasma amino acid imbalance. In the CSF of cirrhotic patients without encephalopathy, a significant increase was found in nearly all amino acids, including those known to not easily cross the blood-brain barrier; this suggests the presence of a nonspecific modification of the blood-brain barrier permeability. In patients with severe hepatic encephalopathy, the further increase only in cerebrospinal fluid aromatic amino acids and methionine levels suggests the presence of a selective stimulation of the neutral amino acid transport system across the blood-brain barrier. Finally, the good correlation between glutamine and the sum of neutral amino acids found in the cerebrospinal fluid only in the presence of encephalopathy supports the hypothesis that brain glutamine may stimulate neutral amino acid transport across the blood-brain barrier.