Distal renal tubular acidosis (RTA) can lead to rickets in children or osteomalacia in adults if undetected. This disorder is normally diagnosed by means of an oral ammonium chloride-loading test; however, the procedure often leads to vomiting and abandonment of the test. In this study, we assess an alternative, more palatable approach to test urinary acidification. This was achieved by the simultaneous oral administration of the diuretic furosemide and the mineralocorticoid fludrocortisone to increase distal tubular sodium delivery, principal cell sodium reabsorption, and alpha-intercalated cell proton secretion. We evaluated 11 control subjects and 10 patients with known distal RTA by giving oral ammonium chloride or furosemide/fludrocortisone in random order on separate days. One control and two patients were unable to complete the study owing to vomiting after NH4Cl; however, there were no adverse effects with the furosemide/fludrocortisone treatment. The urine pH decreased to less than 5.3 in the controls with both tests, whereas none of the patients was able to lower the urine pH below 5.3 with either test. We conclude that the simultaneous administration of furosemide and fludrocortisone provides an easy, effective, and well-tolerated alternative to the standard ammonium chloride urinary acidification test for the diagnosis of distal RTA.