In chronic renal failure (CRF), phosphate (Pi) retention may lead to secondary hyperparathyroidism and progression to end-stage renal disease (ESRD). Dietary phosphorus restriction or phosphate binders can slow progression in experimental CRF. Conversely, diets high in phosphorus can accelerate the progression toward ESRD. Phosphate binders reduce intestinal Pi. absorption but have no effect on its renal excretion. Phosphonoformic acid (PFA, foscar-net) is a specific inhibitor of both intestinal and renal brush border Na+-Picotransport. It causes phosphaturia when administered parenterally or orally to rats. To determine the effect of oral PFA on renal function and on phosphate excretion in renal insufficiency, PFA was administered in drinking water to rats with CRF produced by 5/6th nephrectomy. Blood and 24-h urine collections were performed every 2 weeks for determination of plasma Piand creatinine concentrations, urinary protein excretion, and urinary creatinine and Piclearances. PFA, administered for 8 weeks, did not exert any adverse effects on any of the measured parameters. The slopes of the reciprocal of plasma creatinine versus time were not different between control and PFA-treated rats. Although PFA increased Piexcretion over the baseline, it had no persistent effect on plasma Piconcentrations under these experimental conditions.