Mammalian erythrocytes are known to have 4 distinct amino acid transport systems. The C system is found in sheep erythrocytes and is specific for neutral amino acids of intermediate size. Human cells lack the C system and have two alternative neutral amino acid transport mechanisms: the L system which is selective for large hydrophobic amino acids and a Na-dependent alanine-cysteine system. The L system is absent from ruminant and cat erythrocytes. Human rabbit and cat cells, but not sheep erythrocytes, have a specific dibasic amino acid transport mechanism (Ly system). L-Tryptophan uptake by human erythrocytes is mediated by two routes: a saturable high-affinity transport mechanism selective for L-tryptophan and a low affinity uptake mediated by the L system. The saturable component of L-tryptophan transport occurs by a previously unidentified uptake system, and is the major route for L-tryptophan uptake at physiological substrate concentrations. This system is absent from sheep and cat erythrocytes.