To elucidate the effect of KC 404, an anti-asthmatic agent, on electrolyte transport across airway mucosa, we studied electrical properties of canine tracheal epithelium under isometric conditions in vitro. Addition of KC 404 decreased short-circuit current, transepithelial potential difference and cell conductance, accompanied by the decrease in 22Na flux from submucosa to mucosa. The KC 404-induced decrease in short-circuit current was inhibited by amiloride but not by diphenylamine-2-carboxylate. These results suggest that KC 404 selectively inhibits Na absorption by airway epithelium, thereby leading to the increase in water content in the respiratory lumen.