This presentation addresses the current knowledge of the transport physiology of the thick ascending limb of Henle’s loop (TAL). Novel experimental evidence will be presented that highlight an important role of the TAL in renal acid base physiology. The thick ascending limb of the loop of Henle drives the urinary concentration ability and at the same time permits the excretion of extra water via its ability to dilute the urine. It is critical for the absorption of the divalent cations Ca2+ and Mg2+. By blocking the apical NKCC2 co-transporter the loop diuretic furosemide triggers a marked diuresis and saluresis. In addition, furosemide causes an acute and pronounced urinary acidification and long term application of this diuretic triggers systemic metabolic alkalosis. This furosemide effect is currently explained by an increased Na+ load to the collecting duct, which leads to an increased lumen-negative electrical voltage. This in turn facilitates H+ secretion via the apical H+ ATPase in α-intercalated cells. The direct role of the TAL on urinary acidification has not been thoroughly addressed. In this presentation data will be presented that identify the TAL as a major site of H+ secretion after the application of furosemide. This TAL-dependent H+ secretion/urinary acid excretion is of substantial magnitude and can be specifically blocked by inhibiting the NHE3 Na+/H+ antiporter. These novel results have major implications to understand the pathophysiology of distal renal tubular acidosis (dRTA), a heterogeneous clinical syndrome with the inability to acidify the urine. In dRTA the furosemide test is believed to test the ability of the collecting duct to acidify the urine.