A detailed study has been made of the effect of CO 2 and hydrogen ion on the sodium ion transport system of isolated frog skin. The short-circuit technique has been used as a measure of the net sodium flux, and open circuit potential measurements were made as well. The sodium ion flux was investigated as a function of sodium ion concentration in the solution bathing the external surface at a variety of pH's in the range 6–8. 4. These data were subject to analysis in terms of a model previously proposed and the inhibition of the sodium transport system by H + was found to be interpretable as non-competititve. The sodium ion flux was also investigated following step changes in pH of the bathing solutions as well as changes in buffer system at the same pH. The resulting transient changes in sodium ion flux are interpreted with the aid of a simple model mechanism which accounts for the observed differences in effect between a CO 2HCO 3 buffer and phosphate buffer in terms of the relative rapid diffusion of CO 2 leading to local changes in H + concentration at the site of the transport system.