Multiple studies have noted that obese individuals are at a high risk of renal cell cancer. Similarly, numerous case-control and cohort studies have consistently reported that individuals with a history of hypertension experience an increased risk of renal cancer. In spite of this compelling body of epidemiologic data, no credible hypothesis has been advanced to explain this dual etiologic association. In this communication we propose that lipid peroxidation, which is increased in obese and hypertensive subjects, is the mechanism responsible, at least in part. for their increased risk of renal cell carcinoma. In experimental animals lipid peroxidation of the proximal renal tubules is a necessary mechanistic pathway in renal carcinogenesis induced by several different chemicals. Our hypothesis may also explain the roles of other risk (oophorectomy/hysterectomy, parity, smoking, diabetes) and protective factors (dietary antioxidants) for renal cell cancer.