In premenopausal women with breast cancer, total serum oestradiol (E2) concentrations are normal but nonprotein-bound E2 concentration are significantly raised. This is not due to low sex-hormone-binding-globulin (SHBG) binding capacities which are within the normal range and is unlikely to be due to the small but significant decrease in albumin concentrations. In post-menopausal patients, both total and non-protein-bound E2 are significantly raised: this may be explained partially by lower SHBG binding capacities. In patients and controls there is a highly significant correlation between non-protein-bound E2 and SHBG but, for a given SHBG binding capacity, the patients have more non-bound E2 than controls. It is concluded that the breast in women with breast cancer may be exposed to elevated levels of biologically active E2 although the reasons for this remain obscure.