Levels of circulating estrone (E1), estradiol (E2), androst-4-ene-3,17-dione (Adione), 3,5,3'-triiodothyronine (T3), thyroxine (T4), and sex hormone-binding globulin (SHBG) were measured in 10 obese postmenopausal patients with breast cancer and in 10 obese postmenopausal control subjects matched for age, body size, and menopausal status. T3, T4, and SHBG were also measured in 10 lean postmenopausal control subjects. In cancer patients after mastectomy, the cytosolic estrogen receptors (E2R) in tumor specimens were determined. No significant differences between the two groups of obese postmenopausal women were found for levels of all determinations carried out in serum. Comparing obese subjects (with or without breast cancer) with lean controls, circulating levels of T3 were found approximately 50% higher in the obese group. Conversely, SHBG was found around 50% of the value observed in lean controls. The changes presumably produced by obesity on serum SHBG levels appear to be reversible, tending toward normality with weight reduction. In cancer patients SHBG correlated negatively with cytosolic E2R concentrations (P less than 0.01). In conclusion, it is considered that obesity implies a double risk for breast cancer in susceptible postmenopausal women, by inducing a decrease of SHBG and a concomitant increase of the supply of "free" E2 to target tissues, in absence of cyclic endogenous progesterone.