Plasma estrogen and progesterone levels were determined in 77 premenopausal and 137 menopausal women at the same time that estradiol receptor (ER) and progesterone receptor (PGR) assays were carried out on their breast cancers. The frequency of ER and PGR is approximately the same in premenopausal and postmenopausal women, but the ER content is much higher in postmenopausal women. Although this is usually ascribed to the occupancy of receptors by endogenous estrogen in premenopausal women, our observations suggest that this is unlikely. The higher ER content in postmenopausal women is probably due to the fact that the cyclic progesterone increase in premenopausal women limits estrogen stimulation of ER synthesis. Our data suggest that the circulating levels of estrogen in postmenopausal women are sufficient to stimulate ER and PGR when ER is functional. In premenopausal women, on the other hand, high levels of circulating progesterone may inhibit PGR, and the absence of PGR in the breast cancers of premenopausal women should be interpreted warily if the plasma level of progesterone is unknown.