Intracellular oestrogen metabolism has been investigated in endometrial tissue from postmenopausal women receiving oestrogen therapy either alone or in combination with a progestogen. During oestrogen therapy alone, there was a 3.2 fold predominance of oestradiol over oestrone within the endometrial cell nucleus and the mean nuclear oestrogen receptor content was 1.40 pmol/mg DNA. The addition of norethisterone decreased the nuclear oestradiol/oestrone ratio to 1.4:1 by lowering the oestradiol mass. A concurrent reduction in the mean level of the nuclear oestrogen receptor to 0.58 pmol/mg DNA indicated a decrease in oestrogenic stimulation. The activity of oestradiol-17 beta dehydrogenase was significantly increased. There was a plasma excess of oestrone over oestradiol during oestrogen therapy alone and oestrone/oestradiol ratio was not significantly altered following norethisterone administration. The ability of the endometrium to incorporate oestradiol selectively into the nucleus is discussed in relation to the risk of endometrial hyperplasia with unopposed oestrogen therapy. The profound biochemical changes induced by norethisterone help elucidate mechanisms whereby progestogens lower oestrogenic potency and thereby protect the endometrium against excessive stimulation.