Although recent data have suggested an association between renal cell cancer and the use of diuretics, it remains unclear whether these medications or hypertension is the important risk factor. In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with hypertension and use of diuretics and other antihypertensive medications. Risks increased with the use of diuretics or other drugs that lower blood pressure, especially among persons who reported no history of hypertension. After adjustment for hypertension, the use of diuretics alone was associated with a 40% excess risk (OR = 1.4; 95% CI = 0.8-2.2), while use of other antihypertensive drugs was linked to a 2-fold risk (OR = 2.0; 95% CI = 1.2-3.3). The excess risk was not restricted to any specific products, and no trend was observed with estimated lifetime consumption of any product. Furthermore, risk was not potentiated by the presence of both hypertension and the use of antihypertensive drugs. Among persons who did not use antihypertensive drugs, a history of hypertension was associated with a significant 40-50% excess risk of renal cell cancer. Excluding subjects with hypertension diagnosed within 5 years of cancer diagnosis or interview had only a small effect on risk. These findings suggest small effects on renal cell cancer risk associated with hypertensive disease and with the use of diuretics and other antihypertensive drugs, but it is difficult to disentangle the separate effects due to potential misclassification of highly correlated events.(ABSTRACT TRUNCATED AT 250 WORDS)