Estradiol and progesterone receptors have been characterized in normal human endometrial biopsy samples. The cytosol and nuclei were prepared from 150-250-mg samples, either processed immediately or kept in liquid nitrogen. The total concentration of estradiol-and progesterone-binding sites (available or occupied with endogenous hormone) were measured in both fractions. Results were best expressed in femto-moles per mg DNA, or in sites per cell, assuming an even distribution of receptor throughout the endometrial samples. The contribution to total binding of non-saturable binding components and of plasma proteins (transcortin or sex steroid-binding protein) was taken into account. Measurements were obtained in more than 300 patients, among whom 54 had completely normal menstrual cycles on the basis of clinical, hormonal, and histological features. Total estradiol and progesterone receptors were highest in the late proliferative phase (about 8,000 and 12,000 sites/cell, respectively) and were very significantly lower in the late secretory phase. During the proliferative phase, estradiol receptors were increased only in the nuclear fraction, whereas progesterone receptors were increased mainly in the cytoplasm. In the early luteal phase, estradiol and progesterone receptors decreased in the cytosol, whereas they remained high in the nuclei. Both receptors were at their lowest level in cytosol and nuclei in the late secretory phase. The changes of total estradiol and progesterone receptor sites and of their respective subcellular distributions seem to depend upon the plasma levels of both hormones and to follow the same cause and effect relationships as those demonstrated experimentally in laboratory animals.