Functional indices of distal acidification were assessed in five unrelated children with primary distal renal tubular acidosis. All patients were unable to lower urinary pH below 6.0 both during ammonium chloride-induced acidosis or after acute i.v. administration of furosemide. In these patients the urine minus blood Pco2 gradient failed to increase normally during acute sodium bicarbonate loading (mean +/- SEM: 5.8 +/- 2.0 mmHg), or after neutral phosphate administration (13 +/- 2.7 mmHg), despite adequate urinary concentrations or bicarbonate (72.2 +/- 14.6 mmol/L) and phosphate (25 +/- 2.3 mmol/L), respectively. They also failed to decrease urine pH below 5.5 with sodium sulfate (7.17 +/- 0.08), but urinary potassium excretion increased significantly. These results strongly suggest that the mechanism responsible for defective distal acidification is a failure of hydrogen ion secretion ("secretory' defect) and not an inability to establish a steep hydrogen ion gradient, as it was formerly believed.