The diuretics amiloride, triamterene and the spirolactones have the distinct property of reducing kaliuresis while promoting Na + excretion, in contrast to the members of the two other classes of diuretics, the loop diuretics and the thiazides. The common property of the K+-sparing diuretics is to reduce the electrogenic transport of Na + across the socalled "tight" epithelial that line the distal part of the nephron. This property has been studied extensively in experimental models of tight epithelia such as the skin or urinary bladder of amphibian and in perfused collecting tubules of mammalian kidney [4]. While spironolactone acts by inhibiting the complex action of aldosterone on many effector elements (Na,K-ATPase, apical Na + channel, basolateral K + channels, energetic metabolism) it is well known that amiloride produces its effects by inhibiting a highly Na+-selective channel located in the apical membrane of the epithelial cells. How does amiloride prevent the secretion of K + ? Potassium secretion across the apical membrane is driven by the lumen negative potential difference. As the negative intratubular potential is generated by the electrogenic absorption of Na +, it is easy to understand that blocking Na + transport abolishes the driving force for K + secretion. The tight epithelia lining the distal parts of the nephron and of the colon control the final Na + and K + content of the excreta and are therefore the main effector mechanisms by which the organism controls its global Na + and K + balance. Therefore the regulated function of these epithelia is essential for the maintenance of the extracellular fluid volume and blood pressure. This regulation occurs mainly by modulation of the activity of the apical membrane amiloride-sensitive Na + channel, which is the rate-limiting step in transepithelial Na + reabsorption.