We have measured the three principal oxidative transformations of estradiol by means of a radiometric procedure in women with breast or endometrial cancer and in age matched controls. No difference between the 17 beta-ol oxidation or 2-hydroxylation of the hormone was observed between the study groups. In contrast, 16 alpha-hydroxylation was strikingly elevated in the women with breast and endometrial cancer relative to the age matched controls. Evidence is presented that this increased activity precedes the clinical evidence of the disease and that it represents a significant risk factor for these estrogen dependent tumors. This risk may be mediated by one of the products of 16 alpha-hydroxylation, 16 alpha-hydroxyestrone, which exhibits unique biological properties.