The occurrence of PP12 was studied by the biotin-avidin immunoperoxidase method in the endometrium of 106 premenopausal and postmenopausal women at various phases of the menstrual cycle or during estrogen and progestogen replacement therapy. No PP12 was found in the endometrium under the following conditions: (1) during the proliferative phase, (2) in cystic glandular hyperplasia, (3) during the first 3 postovulatory days in ovulatory cycles, (4) in atrophic postmenopausal endometrium, and (5) in estrogen-stimulated postmenopausal endometrium. PP12 was found in the endometrium under the following conditions: (1) in the secretory endometrium from the fourth postovulatory day onward, (2) in the endometrium during progestogen treatment of previously anovulatory premenopausal women, and (3) in the endometrium from postmenopausal women treated with estrogen followed by combined estrogen and progestogen replacement therapy. These results suggest that PP12 is a P-dependent protein which, in natural cycles, appears in the endometrium around the time of implantation and, in postmenopausal women, can be induced by progestogens after estrogen priming.