The effect of ouabain on urinary Na and K excretion was compared with that of aldosterone by injecting 0.1 or 0.5 mg ouabain or 0.25 micrograms aldosterone. The administration of 0.25 micrograms aldosterone caused sodium-retention without kaliuresis, whereas the administration of 0.5 mg ouabain caused kaliuresis without sodium-retention. These results indicate that ouabain is a kaliuretic agent. The effect of a combination of aldosterone and ouabain was evaluated by injecting 0.25 micrograms aldosterone simultaneously with 0.1 or 0.5 mg ouabain. The combination of aldosterone and ouabain caused both sodium-retention and kaliuresis. These results indicate that ouabain works synergistically with aldosterone to increase mineralocorticoid action by inducing K depletion from the cells in various tissues.