Neutral phosphate infusion results in an elevated urinary minus blood PCO2 gradient (U-B PCO2), providing that the urinary pH is close to the pK (6.8) of the phosphate buffer system. The present investigation was designed to evaluate whether an oral phosphate load could achieve similar results in children. 18 normal children, aged 3-13 years, were studied. Following the oral phosphate load, the urinary phosphate concentration increased to 44.8 +/- 4.7 mmol/l (mean +/- SEM), and U-B PCO2 reached 68.8 +/- 7.0 mm Hg, with a urinary pH of 6.87 +/- 0.07. With a urinary phosphate concentration above 20 mmol/l, all children reached a U-B PCO2 above 40 mm Hg. 4 children with primary distal renal tubular acidosis were also studied. All exhibited a U-B PCO2 below 20 mm Hg despite values of urinary phosphate concentration at or above 20 mmol/l, indicating the presence of a true secretory defect in distal hydrogen ion secretion. The present study demonstrates that an oral phosphate load is as effective as a phosphate infusion in elevating the urinary PCO2 and, therefore, could have a wide application in the pathophysiologic evaluation of renal tubular acidosis.