Experiments performed at 25 degrees C, pH 7.4, confirmed that the human red blood cell possesses both Na-independent and Na-dependent transport systems for neutral amino acids. Further evidence for the existence of a major Na-independent pathway for the large neutral amino acids (L-leucine, L-isoleucine, L-phenylalanine, L-valine and L-methionine), designated the 'L-system', was provided from trans-acceleration experiments of L-leucine efflux. Transport via the L-system with respect to kinetics of substrates and stereospecificity was studied. Experiments on inhibition of transport and on kinetics of Na-dependence of uptake of L-alanine and glycine were consistent with Na-dependent amino acid transport being mediated by two different systems, i.e. an ASC-system for L-alanine, L-serine and L-cysteine and a Gly-system for glycine transport. When compared with a 'high capacity/low affinity' pattern of kinetics of the L-system, Na-dependent uptake of L-alanine and glycine was found to exhibit 'low capacity/high affinity' kinetics. The Na-dependence of L-alanine uptake conformed to first order interaction, that of glycine uptake to second order. An effect predominantly on the maximum transport capacity (V12) of the saturable Na-dependent uptake route of L-alanine and glycine, respectively, by a 50% reduction of the extracellular Na+ concentration, was suggested.