During acylation of benzoate, glycine nitrogen is incorporated into hippurate which can be readily excreted by the kidney. To determine if glycine and urea metabolism are changed during administration of benzoate to patients with chronic renal failure, 10 g/day of sodium benzoate was given to seven patients with an average estimated glomerular filtration rate of 8 ml/min. Nitrogen balance, the urea nitrogen appearance rate (net urea production rate) and hippurate excretion of each patient were measured during a control period and again during the benzoate period. During benzoate administration, hippurate nitrogen excretion increased by 0.68 +/- 0.05 g of nitrogen per day, equivalent to 70 +/- 5% of the benzoate administered; additional hippurate was excreted subsequently, suggesting that benzoate was virtually completely converted to hippurate. With this conversion, there was a decrease in the urea nitrogen appearance rate of 1.52 +/- 0.43 g of nitrogen per day (P less than .02) so that the serum concentration of urea nitrogen decreased by -19 +/- 3 mg/dl (P less than .011). In spite of the excretion of large amounts of glycine as hippurate, there was no significant changes in plasma concentrations of glycine or serine. This suggests that nitrogenous precursors of urea were used for synthesis of glycine and subsequently hippurate, leading to a reduction in net urea production.