The effect of an aldosterone antagonist on the protective action of carbenoxolone sodium on the gastric mucosal barrier has been studied in three dogs with Heidenhain pouches. The net fluxes of hydrogen ion and sodium ion were measured before, during, and after contact with a 10 mM bile acid solution at pH 2, in pouches which had not been treated with drugs, in pouches treated with carbenoxolone sodium and in pouches treated with both carbenoxolone sodium and the aldosterone antagonist, spironolactone. Hydrogen ion back diffusion from, and sodium ion gain by the untreated pouch was increased by 10 mM bile acid solution. Addition to the pouches of either carbenoxolone sodium alone or carbenoxolone sodium and spironolactone reduced the hydrogen ion back diffusion after exposure to the bile acid solution. The spironolactone did not change the protective effect of carbenoxolone on the gastric mucosal barrier. Carbenoxolone did not change the increased sodium ion diffusion caused by bile.