Abstract Coordinated estrogen- and progesterone-induced changes regulate biological functions of the endometrium. The uterine deciduoma reaction is used as a model in defining the mechanism of the progesterone-induced endometrial transformations. Uterine progesterone concentrations were determined by radioimmunoassay during three critical periods related to progesterone action: the preparatory period, the initiatory period, and the proliferative period. Tissue progesterone concentration significantly exceeded peripheral plasma concentration during the late afternoon of proestrus and in pseudopregnant animals on the day of maximal sensitivity to deciduoma induction. On the basis of the uterine progesterone concentration at the time of trauma, it was possible to predict whether or not decidualization would occur. Thus, substantiation was obtained for the existence of a specific uterine progesterone receptor, and its presence was related to prior exposure of the uterus to estradiol-17β. Summarized evidence for the existence of specific progesterone binding proteins in uterine tissue from several mammalian species, including the human being, shows a fair degree of uniformity in the properties of these binding proteins, e.g., tissue specificity, ligand specificity, and sensitivity to estrogen stimulation. Although some questions remain as to whether the effectiveness of progesterone therapy in endometrial adenocarcinoma can be considered as being proportional to the degree of resemblance of the cancer to normal endometrium, it is suggested that the possibility of such a relationship makes highly desirable the organization of programs designed to correlate the presence of progesterone receptor with progesterone responsiveness in these tumors.