In etiological studies of renal cell carcinoma, the associations between exogenous hormones, reproductive factors, or gynecological operations have not been well examined. Our aim was to evaluate gender-specific risk factors for renal cell carcinoma using data from a population-based case-control study conducted in Los Angeles, California and to elucidate possible underlying mechanisms. A population-based case-control study involving 422 female renal cell carcinoma patients, ages 25-74 years, and an equal number of sex-, age-, and race-matched neighborhood controls was conducted in Los Angeles, California. Detailed information regarding reproductive history, hysterectomy, use of exogenous estrogens, and other medical and lifestyle factors was collected through in-person interviews. Compared to women with an intact uterus, those who had undergone hysterectomy were at an increased risk for renal cell carcinoma (odds ratio, 1.8; 95% confidence interval, 1.3-2.5). Parity and use of estrogen replacement therapy were no longer risk factors for renal cell carcinoma when hysterectomy was adjusted for in the analysis. No association between renal cell carcinoma and use of oral contraceptives was found. Limited epidemiological data do not support an endocrine explanation for the observed hysterectomy-renal cell cancer association. We conjecture that unintentional injury to the ureter during the surgical procedure, which results in renal cell damage and consequent renal cell proliferation, may be a cause of the increased cancer risk in hysterectomized women.