Results from a population-based case-control study of cancer of the renal pelvis and ureter are reported. Telephone interviews were conducted with 187 residents of Los Angeles County diagnosed with cancer of the renal pelvis and ureter over a 4-year period ending December 31, 1982, and with individually sex-, age- and race-matched neighborhood controls. The major risk factor identified for cancer of the renal pelvis and ureter was cigarette smoking. Subjects who smoked more than 25 years had a relative risk of 4.5 of developing these tumors, compared to nonsmokers (P less than 0.0001). Heavy use of over-the-counter analgesics was also associated with a significant increase in risk; it appears that an elevated risk was conveyed by all the major active constituents of those compounds currently marketed in the United States, aspirin, caffeine, and acetaminophen. Persons who had used these drugs for 30 consecutive days at any time in their life preceding diagnosis had twice the risk of developing cancer of the renal pelvis or ureter compared to persons not reporting such use (P less than 0.01). Heavy coffee drinkers (greater than or equal to 7 cups/day) had a 1.8-fold increase in risk compared to nondrinkers. Although risk tended to increase with increasing consumption, this result was not statistically significant. The risk associated with heavy coffee consumption was reduced to 1.3 after adjusting for smoking. Nine cases compared to no controls reported a first degree relative with kidney cancer. A history of kidney stones was associated with an increased risk of cancer of the ureter (relative risk = 2.5) that was not, however, statistically significant.