The authors examined the relation of hypertension, use of diuretics, and use of antihypertensive medications to the risk of fatal renal cell cancer in a prospective cohort study of 998,904 adult Americans followed for 7 years (1982-1989). Analysis included 335 renal cell cancer deaths (123 in women and 212 in men). Cox proportional hazards modeling was used to calculate rate ratios. Increased rate ratios were present for cigarette smoking in men and for elevated body mass index in both sexes. Significantly increased age-matched rate ratios, independent of smoking and body mass index, were present for hypertension, use of diuretics, and use of hypertension medications, but only for women. Multivariate testing confined these risks to hypertensive women who were using hypertension medications alone (rate ratio = 2.2, 95% confidence interval 1.4-3.5) or with diuretics (rate ratio 2.5, 95% confidence interval 1.5-4.3). Risk was not significantly increased for either men or women who had untreated hypertension or who used diuretics alone with or without hypertension. These findings partly support those of earlier studies suggesting that medications related to treatment of hypertension, or the severity of hypertension itself, may contribute to the etiology of renal cell cancer.