We examined the response of 8 patients with nephrotic syndrome (creatinine clearance 70.4 +/- 16.0 ml/min) to oral furosemide (F; 40 mg) in the absence (control) and in the presence of oral hydrochlorothiazide (HCT; 100 mg). In the 24-hour period after oral F, HCT was shown to increase urine volume and urinary sodium and chloride excretion. Increment was most significant during the 12- to 24-hour period. Enhancement of the diuresis with HCT was associated neither with a significant increase in the area under the curve of plasma F concentration nor an increase in urinary F excretion. Urinary excretion of glucuronidated F, one of the main metabolites of F, however, was decreased with HCT. In summary, HCT significantly enhanced the response to F in nephrotic patients.