Introduction The concerted operation of several amino acidtransport systems ensures the optimal composition of the intracellular compartment as well as inter-organ amino acid flow [ l ] . The operation of these transport systems is linked through substrates accumulated by active transport systems (such as Systems A and X,;;) and then exchanged with other amino acids through exchange pathways (Systems L, ASC and &-) [2-41. Glutamine is an ideal substrate for the co-ordinated operation of transport systems for neutral amino acids. Indeed, this amino acid is a good substrate for System A but can also interact with Systems ASC and L [5,6] as well as with specific N-type transport systems, originally described in the liver [7] but also characterized in some mesenchymal models [8]. In the intracellular compartment, 1,-glutamine can be easily converted into 1.-glutamate. However, the intracellular pool of 1.-glutamate can also be fuelled through specific transport routes, such as System X,;; [9,10], an active transport mechanism which has the same operational features of the Na+,K+dependent glutamate carriers, cloned from nervous system and absorptive epithelia [ 1 1 131. Thus the high intracellular concentrations of glutamine and glutamate found in mesenchymal cells [ 141 are the result of the operation of both System A (through glutamine uptake) and System X,; (through glutamate uptake). In mesenchymal cells the kinetic features of these two mechanisms are very different; the V,,, of System A is much higher than that of System X,;; [2]; conversely, the affinity of System A for its substrates is much lower than that of System X,;;. Mammalian cells are usually cultured in media that contain high concentrations of glutamine and little glutamate, a situation resembling that observed in extracellular fluids in viva [ 15,161. Under these conditions, mesenchymal cells accumulate glutamine through System A