To evaluate renal pelvis and ureter (RPU) cancer risk in relation to lifetime use of analgesics, a population-based case-control study was carried out in 3 areas of the United States. Among 502 cases and 496 controls diagnosed and interviewed during 1983-1986, no significant increases in risk were found for any of the non-prescription and prescription analgesics evaluated or among regular users of phenacetin, acetaminophen or aspirin. Neither cumulative lifetime ingestion nor duration of regular use of these 3 drugs, whether alone or in combination, was associated with significantly increased risk of RPU cancer, although a slight excess was observed among long-term users of acetaminophen. Risk was not increased among persons reporting highest cumulative dose and/or longest duration of phenacetin use. Although our study of RPU cancer is the largest to date, it was nonetheless limited by the small number of regular analgesic users and the relatively low response rates. Because of the relatively recent onset of widespread use of acetaminophen, its pharmacologic similarity to phenacetin, a known urothelial carcinogen, and the elevation in risk seen in long-term users, further surveillance of this analgesic is warranted.