A population-based case-control study of renal pelvis and ureter cancers (502 cases, 496 controls) conducted in three areas of the United States found cigarette smoking to be associated with a 3.1-fold increase in risk, with long-term (greater than 45 years) smokers having a 7.2-fold increased risk. Statistically significant dose-response associations were observed for both cancer sites and in both sexes regardless of the measure used: cigarettes per day, duration of use, or pack years. A significant decreasing trend in risk with increasing years quit smoking was also demonstrated for these cancers. Attributable risk estimates indicate that approximately 7 of 10 cancers of the renal pelvis and ureter among men and almost 4 of 10 among women are caused by smoking. The results of this study, the largest to date, confirm that cigarette smoking is the major cause of cancers of the renal pelvis and ureter, and that cessation of smoking could eliminate a large proportion of these tumors.