To understand ectopic hormone secretion in cancer we compared the plasma concentrations of the hCG-like substance in normal nonpregnant subjects and in women with breast cancer. In 45 normal men the plasma concentrations did not vary with age (median, 5 pg/ml; range, less than 3-169) whereas in 45 normal women they increased after menopause (median, 48 pg/ml; range, less than 5 -569, n = 20, P less than 0.0001). In 56 women with breast cancer the plasma concentrations of the hCG-like substance after menopause were much higher than in normal women (median, 202 pg/ml; range, 14-1561; n = 35; P less than 0.001), with no abnormally high pituitary gonadotropin values and no relationship with the tumor burden (same median after mastectomy, 198 pg/ml; n = 21). This hCG-like substance was glycosylated and similar to standard hCG according to molecular size, ionic strength, and immunoreactivity. Our data are compatible with the following conclusions: 1) the plasma concentration of the hCG-like substance is normally very low but dependent on gonadal function in women. Its source might be the pituitary gland or peripheral tissues. 2) Its concentration is much increased in postmenopausal women with breast carcinoma. This increase is found with normal pituitary gonadotropin values and is independent of the tumor burden, suggesting it is of extrapituitary and nontumoral origin.