Although women with breast cancer tend to have a greater proportion of their circulating oestradiol non-protein bound and albumin bound, and less SHBG-bound, than controls, it remains uncertain whether this has an aetiological role or is an effect of the tumour. Oestradiol and its binding to serum proteins was investigated: (a) in relation to risk factors for breast cancer in a normal population; (b) in women with proliferative benign breast disease as a risk group for breast cancer, and women with non-proliferative benign breast disease as a low risk group, as well as breast cancer patients. The strongest associations were with body mass index; the greater the body mass the greater the bioavailability of oestradiol. Changes in relation to age at menarche and menopause could have been a function of body mass. An interesting change with age was noted with a fall in bioavailability over the menopausal years. There was no relationship apparent for parity, age at first full term pregnancy, family history or country of birth. Similar differences in oestradiol binding between cases and controls were seen for patients with breast cancer, benign epithelial hyperplasia and fibrocystic disease without proliferative changes, but these were not significant. This study provides limited support for the concept that oestradiol binding has an aetiological role in the development of breast cancer.