The presence of a progestogen-dependent endometrial protein (PEP) in women was previously described. The present study was undertaken to determine whether the occurrence or the concentration of PEP in endometria is related to the developmental stage of tissues and/or to the levels of endogenous progesterone (P) or 17 beta-estradiol (E) to which the tissues are exposed. Samples of serum and endometrial tissue in different developmental stages were obtained from pregnant women and women with normal menstrual cycles and were analyzed for PEP. In addition, the sera were analyzed for P and E. The occurrence of PEP in the endometrium of all of the women who were studied was found to be correlated with the heightened secretory activity and with the decidual change in the tissue. Furthermore, in women with normal cycles, the detection of PEP was associated with high serum levels of P. Comparison of serum levels of P with endometrial levels of PEP in pregnant women and in women in the mid-secretory phase of the menstrual cycle indicated that a 2.8-fold rise in serum levels of P during pregnancy was accompanied by a comparable (about threefold) rise in tissue levels of PEP. Therefore, we conclude that, in pregnant women and women with normal cycles, the levels of PEP in the endometrium reflect developmental changes within the endometrium, and that those levels are directly related to serum levels of P.