Furosemide stimulates urinary acidification in normal humans probably by increasing distal Na delivery and transport, thus creating a favorable electric gradient for H+ and K secretion. Therefore, furosemide should stimulate urinary acidification in patients with distal renal tubular acidosis, provided the distal nephron is capable of transporting Na and the H+ pumps can respond to the favorable electric gradient. We examined the effect of short-term furosemide administration on urinary acidification in five normal participants and 12 patients with normokalemic, hypokalemic, or hyperkalemic distal renal tubular acidosis. In controls, furosemide decreased urine pH and increased net acid and K excretion. In six of eight patients with normokalemic or hypokalemic renal tubular acidosis, furosemide decreased urine pH and increased net acid and K excretion to levels not significantly different from control values. The patients that had normal responses were interpreted as having a rate-dependent or gradient distal renal tubular acidosis, and thus increased distal Na delivery created a favorable electric gradient for H+ and K secretion. The normokalemic patients who did not have a response were considered to have a defect in the pumps (secretory defect). Of the four hyperkalemic patients, two had a voltage-dependent defect and the other two had aldosterone deficiency. The patients with selective aldosterone deficiency had low baseline urine pH values that did not change with furosemide administration, but net acid and K excretion did increase significantly. The patients with voltage-dependent defect did not lower urine pH or increase net acid and K excretion. Our data demonstrate that administration of furosemide enhances urinary acidification in certain patients with distal renal tubular acidosis. We suggest that furosemide administration may be useful in the characterization of the mechanism responsible for distal renal tubular acidosis and in the treatment of distal renal tubular acidosis in selected patients.