The pattern of free amino acid in tissues is quite different from the pattern in plasma. The gradients between extracellular and intracellular space is highly variable and range from 1 to almost 1000. The amino acids with the highest ratio are taurine and glutamate. At the other end of the span we have amino acids with a small gradient, usually essential amino acids such as phenylalanine. Cysteine is a special case where we have the oxidised and reduced forms and the majority of the cysteine in blood is stored into the erythrocytes. This normal pattern of free amino acids in muscle is a reflection of protein synthesis and degradation, interorgan transplantation of free amino acids as well as amino acids transported across the cellular membrane. It is also a reflection of denovo synthesis and break down or oxidation of the free amino acids. Taking into account the many inputs and outputs, the intracellular free amino acid concentrations is remarkable stable. Physiological changes in the normal state, such as defect of feeding, only gives marginal effects on the intracellular concentration although the plasma concentrations may change considerable. In general terms there are two major differences between the healthy individuals and the ICU patients. 1) The low concentrations of glutamine, glutamate and the basic amino acids. 2) The comparatively high concentrations of the branched chain amino acids and the aromatic amino acids. In particular the concentration of glutamine is very low compared to healthy individuals, 20 – 25 % of normal value. Although these patients also have a low plasma glutamine concentration, the gradient is also lower than normal. This low value appears early in the course of ICU stay and is rather unaltered also during a long stay in the intensive care unit. There are evidence that the denovo synthesis of glutamine in muscle is not different from normal, this is reflected in the endogenous rate of appearance which is reported to be in the normal range also when a depletion in plasma or intracellular is muscle is seen. The effects of the low values of the basic amino acids, lysine, histidine and arginine, is less well known. It is highly unlikely that the depletion of arginine will have an effect upon NO-production. This is however a matter of controversy, in particular as iNO may respond to substrate availability. The higher than normal levels of the branched chain and aromatic amino acids are thought to be a reflection of the increase in protein break down. These amino acids are not denovo produced in muscle, as they are essential. In particular the branched chain amino acids are usually oxidised to large extent in skeletal muscle. This seems to happen to a lesser degree in ICU patients. Among the aromatic amino acids in particular phenylalanine is often increasing over time. And the balance of phenylalanine across the leg is sometimes used as an indicator of muscle protein depletion. The free amino acids in muscle in intensive care unit patients show a specific and reproducible pattern. The interpretation of this pattern is not yet fully understood. Availability of the different amino acids seems to have little impact on this pattern and the restoration back to normal takes a long time.