Studies have been conducted using isolated surviving skin of Rana temporalia in an attempt to evaluate the effect of N-ethylmaleimide (NEM) on the epithelial Na⁺ transport. Active transport of Na⁺ across the skin was estimated by measuring short circuit current (SCC). NEM administered to the outside surface of the skin in concentration of 0.5 X 10^-4-2.5 X 10^-4M induced 20~40% increase during the first 30 mintues, followed by a gradual reduction in SCC. With NEM above 4 X 10^-4M, SCC was inhibited from the beginning. Qualitatively similar results were obtained when NEM was added to the inside bathing medium. However, the concentration of NEM for a similar effect was much higher with the drug in the inside bathing medium than in the outside bathing medium. The oxygen consumption of the skin was inhibited by NEM of above 10^-4M, the effect being of approximately the same magnitude as that on SCC. The activity of Na⁺-K⁺ ATPase of the skin was not inhibited by NEM below 10^-3M, but it was dramatically reduced with 1.2 X M NEM. The effects of NEM (10^-4M) on the SCC and oxygen consumption could be eliminated by adding cysteine (10^-4-10^-3M) in the medium, indicating that the SH group is involved in the action of NEM in the frog skin. On the basis of these results, the mode of action of NEM on the Na⁺ transport across the frog skin was discussed.