The standard test for the diagnosis of distal renal tubular acidosis (dRTA) is to determine whether urine pH falls appropriately (to <5.5) in response to the administration of an acid load in the form of oral NH₄Cl, usually given as a single dose (Wrong & Davies, 1959). However, NH₄Cl capsules in the quantities required are unpleasant to ingest and frequently lead to vomiting and abandonment of the test. The present study has assessed an alternative and more palatable test of urinary acidification. The loop diuretic frusemide increases the delivery of sodium to the distal tubule and collecting ducts, which stimulates electrogenic sodium reabsorption in those nephron segments, thereby favouring H⁺ secretion (Batlle, 1986). In our study, frusemide was combined with the synthetic mineralocorticoid fludrocortisone, which, in addition to stimulating sodium reabsorption, directly stimulates H⁺ secretion by α-intercalated cells. Ten patients with previously diagnosed dRTA were given orally, on separate occasions and in random order, either NH₄Cl capsules (100 mg/kg) or fludrocortisone (1 mg) plus frusemide (40 mg). Urine was collected hourly for the next 8 h and its pH measured with a glass electrode. This protocol was repeated in a control group of subjects comprising five healthy volunteers and five patients with recurrent renal calculi. Of the original cohort of subjects, one control and two dRTA patients were unable to complete the study due to vomiting after NH₄Cl loading; no one experienced side effects from the frusemide/fludrocortisone test. In the remaining members of the control group (n=9), urinary pH fell below 5.5 within 7 h in all subjects with the frusemide/fludrocortisone test (minimum pH = 4.79 ± 0.30; mean ± SEM) whereas 3 control subjects failed to acidify their urine below pH 5.5 with the NH₄Cl test (minimum pH = 5.23 ± 0.45). This difference was statistically significant (P<0.05, Student’s paired t test). In the dRTA group (n=8), no patient was able to lower their urinary pH to 5.5 after either test (frusemide/fludrocortisone, minimum pH = 6.75 ± 0.28; NH₄Cl, minimum pH = 6.50 ± 0.40; NS). We conclude that the combination of frusemide and fludrocortisone provides an effective, well-tolerated alternative to the standard NH₄Cl urinary acidification test.