To assess the hypothesis that a history of vasectomy is a risk factor in the etiology of prostate cancer, the authors conducted a case-control study at Roswell Park Memorial Institute, Buffalo, NY, between 1982 and 1988. From epidemiologic data routinely collected from entering patients, information on vasectomy history and other data were obtained for 614 patients with prostate cancer and 2,588 comparable control subjects with cancer at another site. Age-specific and age-adjusted relative risks were calculated. Increased risk (relative risk = 1.7, 95% confidence interval 1.1-2.6) was found for reporting vasectomy at any age. Age-adjusted relative risk of 2.2 (95% confidence interval 1.0-4.6) was observed for men who reported vasectomy 13-18 years before diagnosis. A significant trend in the association of years since vasectomy and risk also was observed. Cases and controls were found to be nearly identical with respect to education, income, race, marital history, and number of children. A difference in smoking histories of cases and controls was found not to confound the observed associations. These data may suggest the importance of further epidemiologic and biologic research on vasectomy as a risk factor for prostate cancer.