After severe trauma or disease glutamine (GLN) is mobilised from all muscles, including the heart and smooth muscles. The result is weakness and fatigue which affects recovery. The breakdown of muscle tissue can be counteracted by external GLN supply. There are concerns, however, that increasing the blood glutamine (Blood-GLN) concentration in patients with acute brain diseases is harmful by elevating the CNS interstitial (IS) concentration of glutamate (CNS-GLT), and that this may result in a secondary excitotoxic injury. We therefore studied the IS CNS-GLN and CNS-GLT when a commercially available nutritional amino acid solution was given intravenously. Ten NICU patients were included. The IS concentrations of amino acids in the brain were measured using intracerebral microdialysis. Blood concentrations of amino acids were measured before and after the amino acid infusion. The change in Blood-GLN was 2.14 (median; range 1.34-3.22) times the basal levels and Blood-GLT increased 1.37 (median; range 0.93-3.45) times basal levels. Both changes were statistically significant. The changes in CNS-GLN was 1.21 (median; range 0.72-1.92) and for CNS-GLT 0.96 (median; range 0.45-1.53) times the basal levels. This was statistically significant for CNS-GLN but not for CNS-GLT. A high initial CNS-GLT (55.3 micromol/l) in one patient increased even further to 84.4 micromol/l after infusion of amino acid solution. We submit that nutritional amino acid solutions can be administrated to some patients with acute brain disease without increasing the CNS-GLT values. However, since BBB function was not quantified in our study, further evaluation of this issue is warranted.