1. Erythrocytes were incubated in buffers with different [bicarbonate]/[chloride] ratios.
2. The erythrocyte sodium content was higher in buffers with higher [bicarbonate]/ [chloride] ratios.
3. The rise in erythrocyte sodium concentration with increase in [bicarbonate]/[chloride] ratio was independent of the effects of ouabain and ouabain plus ethacrynic acid. Primaquine-induced changes in membrane permeability, ATP depletion by starvation and the use of potassium-free buffers did not change the effect.
4. The results may demonstrate a system which either increases the permeability of erythrocytes to sodium or regulates the sodium content of erythrocytes by a carrier system which is independent of ATP.