The sine qua non for the diagnosis of distal renal tubular acidosis requires that the urinary pH cannot decrease maximally during systemic acidosis. A defect in distal acidification however, could also result from a decrease in the capacity (or rate) of distal hydrogen ion secretion. In this type of defect, the ability to lower the urinary pH during acidemia could be preserved as long as a certain capacity for hydrogen ion secretion remained. In this report, we describe four patients with deranged distal urinary acidification, in whom urinary pH was able to decrease (4.99 +/- 0.11) during acidemia. One of the patients had hyperchloremic metabolic acidosis whereas the remaining three were not spontaneously acidotic. In these patients, the defect for distal urinary acidification was disclosed by the inability of the urine-blood pCO2 gradient to increase normally (i.e., above 30 mm Hg) during bicarbonate loading. In contrast, a normal increase in the urine-blood pCO2 gradient was observed in each patient in response to neutral sodium phosphate infusion. The reabsorptive capacity of bicarbonate was not depressed in these patients, which indicated that the acidification process in the proximal nephron was intact. We propose that our four patients had a defect in distal urinary acidification caused by a reduction in the rate of distal hydrogen ion secretion rather than an inability to generate a steep pH gradient across the distal nephron. Our data also suggest that the inability to raise urinary pCO2 normally during sodium bicarbonate loading may be the most sensitive index of decreased distal urinary acidification available.