Large neutral amino acids compete for transport across the same saturable carrier across the blood brain barrier; an increase in the arterial levels of aromatic relative to branched-chain amino acids may thus cause brain dysfunction through increased intracerebral formation of so-called ‘false’ neurotransmitters that inhibit central noradrenergic pathways (Berg et al, 2010). A reduction in Fischer’s ratio ([valine+leucine+isoleucine]/[phenylalanine+tyrosine]) is therefore thought to cause encephalopathy in fulminant hepatic failure and sepsis. Because these conditions are often associated with arterial hypoxaemia, but it is unknown whether this contributes to changes in the transcerebral exchange of large neutral amino acids. Eleven healthy males aged 27 (mean; SD 4) years were examined in normoxia and following 9h passive exposure to hypoxia (12.9% O2). Global cerebral blood flow (CBF) was measured using the Kety-Schmidt technique, and arterial-to- jugular venous differences of large neutral amino acids were determined at both conditions by high-performance liquid chromatography. Cerebral delivery and net exchange of amino acids were then calculated by multiplying CBF with the arterial concentrations and arterial-to-jugular venous differences of amino acids, respectively. Data are reported as median (interquartile range), and conditions were compared by Wilcoxon’s signed rank test. Hypoxia was associated with an increase in the arterial levels and cerebral delivery of both the aromatic amino acid phenylalanine, and the branched-chain amino acids leucine and isoleucine (Table). Fischer’s ratio was thus unaffected (normoxia: 4.8 [4.5-4.9; hypoxia: 4.6-5.0; NS), and a net cerebral uptake of leucine and isoleucine was maintained during hypoxia with no changes in the cerebral net exchange of phenylalanine (Table). Although inspiratory hypoxia increases the cerebral delivery of the aromatic amino acid phenylalanine, the concurrent increased cerebral delivery of branched-chain amino acids renders the transcerebral exchange kinetics of large neutral amino acids unchanged. Our data thus suggest that arterial hypoxaemia is not critical to the changes in the transcerebral exchange kinetics of large neutral amino acids that occur in fulminant hepatic failure and sepsis.