The availability of specific potassium channel blockers has made it possible to examine their effects along the nephron on fluid and electrolyte excretion. Recent experiments indicate that they modulate transepithelial sodium and potassium transport. In the thick ascending limb, potassium channel blockers, by interfering with potassium recycling across the apical cell membrane, reduce the activity of the sodium-2chloride-potassium cotransporter. In the initial and cortical collecting duct their inhibitory action on ATP-sensitive potassium channels reduces potassium secretion. Accordingly, tissue-specific potassium channel blockers are promising diuretic agents that may induce diuresis by inhibiting tubular sodium transport with only minimal loss of potassium.