Abstract Inhibition of uptake of cationic amino acids by certain neutral amino acids in the presence of alkali metal ions has been studied in the Ehrlich ascites tumor cell, in the rabbit reticulocyte and in yeast. When a hydroxyl group is introduced on carbon 4 (for the reticulocyte) or carbon 5 (for the Ehrlich cell) of straight chain amino acids, a sharp shift in the selectivity among the alkali metal ions occurs in favor of Na+ or of Na+ and K+ in the two animal cells. This shift is associated with attainment of a maximal interaction between the neutral amino acid and the alkali metal, and is taken to support a bridging by the ion between the amino acid and the receptor site. Although in both potassium-treated and glucose-treated yeast neutral amino acids also become much more inhibitory to cationic amino acid uptake in the presence of alkali metal ions, no augmentation has been observed on introduction of a side chain hydroxyl group, and selectivity among the ions is weak. Hence a bridging function is doubted for that organism. The ions exert additional inhibitory effects, independent of the presence of a neutral amino acid, which appear to be competitive with H+.