The excretion of nephrogenic uric acid in the urine of Sprague-Dawley rats was estimated by use of the isotope-dilution technique. In nonfasted rats the urine-to-plasma specific activity ratio (SAR) of [14C]uric acid was 0.93, suggesting that a minimum of 7% of the uric acid excreted in the urine is synthesized in the kidney. During hypoxanthine infusion the SAR decreased in a dose-related fashion, indicating that the rat kidney is capable of synthesizing relatively large amounts of uric acid and that circulating precursor levels may in part regulate the renal synthesis of uric acid. During allopurinol infusion the SAR increased to 1.0, demonstrating that the SAR is a valid indicator of the contribution of nephrogenic uric acid excreted into the urine. Results of perfusion studies in isolated rat kidneys suggest that uric acid is the major end product of purine catabolism in the rat kidney and that some uric acid formed in the kidney may be absorbed directly into the circulation.