Human over-use of analgesics containing phenacetin, antipyrene (phenazone) and caffeine has been associated with the development of both renal pelvic and bladder tumors. In Sprague-Dawley rats antipyrene has been shown to be a weak complete urinary tract carcinogen. The present study was designed to evaluate the promoting capacity of antipyrene in N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT)-induced urinary tract carcinogenesis. One hundred and eighty male Sprague-Dawley rats were divided into groups of 30 and were treated with the following chemicals in the diet: group 1 received a control diet without chemicals; group 2 was treated with 0.2% FANFT in the diet for five weeks followed by control diet; group 3 received 0.2% FANFT for five weeks followed by 0.535% antipyrene in the diet; group 4 was treated with 0.535% antipyrene; group 5 was treated with 0.102% caffeine; and group 6 was treated with 0.535% antipyrene and 0.102% caffeine in the diet. Ten of 27 rats in group 3 (37%) developed urinary tract tumors (P greater than 0.001, five of which were renal pelvic tumors and five were bladder tumors. The majority of the tumors were well differentiated non-invasive urothelial carcinomas. None of the rats in other groups developed urinary tract tumors. In addition, renal papillary necrosis (RPN) was found in 33% of the rats in group 3, 50% in group 4, and 10% in group 6. The present study clearly shows that antipyrene acts as a promoter of FANFT-induced urinary tract carcinogenesis and that it is nephrotoxic to the renal papilla resulting in renal papillary necrosis.