The modest effect of cigarette smoking on renal cell carcinoma (RCC) requires a study with a large number of subjects to definitively answer the question of whether smoking is causally related to RCC. A population-based case-control study was conducted in Los Angeles, California that involved 1204 RCC patients and an equal number of neighborhood controls who were matched to the index cases by sex, date of birth (within 5 years), and race. Detailed information on tobacco use was collected through in-person interviews. Cigarette smoking was associated with a statistically significant 35% increase in the risk of RCC [odds ratio (OR), 1.35; 95% confidence interval (CI), 1.14-1.60]. The risk increased with increasing number of cigarettes smoked per day (two-sided P < 0.001, linear trend test). Former smokers (OR, 1.24; 95% CI, 1.02-1.50) had a lower risk of RCC than current smokers (OR, 1.53; 95% CI, 1.23-1.90). Compared with current smokers, those who quit smoking 10 or more years ago experienced a statistically significant 30% reduction in the risk of RCC. Current smokers who smoked 40 or more cigarettes/day experienced a nearly 2-fold increase in the risk of RCC compared with lifelong nonsmokers. The association between cigarette smoking and RCC was similar in men and women. There were no measurable differences in the risk of RCC between filtered and nonfiltered cigarette smokers or between those who inhaled cigarette smoke deeply and those who inhaled lightly after adjustment for the number of cigarettes smoked per day and current smoking status. After the effect of cigarette smoking was accounted for, heavy cigar smokers (14 or more cigars/week) exhibited a statistically significant 70% increase in the risk of RCC, but no increased risk of RCC was observed for the use of pipes or smokeless tobacco. Seventeen percent of RCC (21% in men and 11% in women) in Los Angeles, California can be attributed to cigarette smoking.