A population-based case-control study of renal cell carcinoma (495 cases and 697 controls) in the Minneapolis-St. Paul seven-county metropolitan area implicated cigarette smoking as a risk factor with an odds ratio (OR) among men of 1.6 (95% confidence intervals: 1.1-2.4) and among women of 1.9 (1.3-3.0). A statistically significant dose response was observed in both sexes for pack-years of cigarette use. On the basis of calculations of attributable risk, it was estimated that 30% of renal cell cancers among men and 24% among women were due to smoking. High relative adult weight as measured by the body mass index (BMI) was found to be a major risk factor among women but not among men, with those in the highest 5% of the BMI having an OR of 5.9 (1.8-20.4) in comparison to the lowest quartile. This association with excess weight was not seen at age 20, but it became more pronounced with increasing age, suggesting that the primary influence of weight gain is during the late stages of renal carcinogenesis. Excess risks were also related to ethnic background (particularly, German), which may account in part for the elevated incidence of renal cancer in the North Central area of the United States. In addition, positive associations were observed for long-term use of phenacetin-containing analgesics, heavy meat consumption, and heavy tea drinking (females only). An occupational clue was provided by an increased risk for exposure to petroleum, tar, and pitch products. Excesses of certain urologic and cardiovascular diseases were also observed among the cases compared to controls.