Loop diuretics such as furosemide, piretanide, and bumetanide bind reversibly to the Na+2Cl-K+ carrier. This transporter is responsible for the uptake of Cl- into the thick ascending limb segment. As a consequence, these compounds reduce or abolish NaCl reab-sorption in this nephron segment and lead to a decreased interstitial hypertonicity and thus to a reduced water absorption. Apart from these profound effects, loop diuretics also inhibit Ca2+ and Mg2+ reabsorption in the thick ascending limb in a manner which is still not clear. They also increase urinary K+ excretion by an increase in distal tubule NaCl and water delivery and probably also by the reduction of K+ reabsorption which goes on under in vivo conditions in the thick ascending limb segment. Finally, by the reduction of the transport work in the thick ascending limb, these compounds reduce dramatically the substrate and oxygen dependence of this nephron segment.