With a view to investigating the mechanism of the action of estrogen involved in nidation, the biologically active rat uterine RNA thereby derived was extracted and then administered in the uterine cavity of castrated rats to observe the ensuing morphological changes in the endometrium and compare them with those resulting from the administration of decidual RNA which is non-estrogenised. There was a tendency toward increasing proliferation noted in the endometrial epithelium of the castrated rats 48 hours after the administration of the biologically active uterine RNA, as in the endometrial epithelium of animals receiving estradiol-17beta. There was also an increase in the number of 3H-thymidine-labelled cells present in the endometrial epithelium of animals so treated. On the other hand, no such changes were observed following the administration of the RNA pretreated with RNase. In the case of castrated rats administered with the RNA in the uterine cavity under progesterone priming, the endometrial epithelium as the site of increase in the number of the radio-labelled cells at 24 hours was found to be superseded by the stromal cells at 48 hours. A similar phenomenon of transfer was seen with regard to the site of an increase in the mitosis index caused by pretreatment with colchicine. An observation of the endometrium of castrated rats 72 hours after the administration of decidual RNA disclosed that the stroma was mildly edematous with the stromal cells somewhat swollen, but without any such changes in the endometrial epithelium as seen following the administration of the biologically active uterine RNA. These findings led us to administer such biologically active substances as uterine RNA, decidual high molecular RNA, human chorionic RNA, rat placental RNA (L15) and early pregnant rat uterine RNA (L4) separately in the uterine cavity of delayed implantation rats to determine whether any one or more of these RNAs had a nidation promoting effect just like estrogen. As a result, nidation was found to be induced in animals administered with 1 approximately 100 microgram of the biologically active uterine RNA or 100 microgram of early pregnant rat uterine RNA. No nidation was provoked by other specimens of RNA. A study was then made of blastocysts recovered by the flush-out technique from the uterus of animals receiving 1 approximately 10microgram of human chorionic RNA or 10microgram of rat placental RNA, which failed to induce nidation. It was shown that these blastocysts were dormant morphologically. From these results it is apparent that both biologically active uterine RNA and early pregnant rat uterine RNA are effective in promoting nidation. It is also suggested that, in the process of implantation of fertilized eggs, nidatory estrogen may first promote RNA synthesis in the endometrium and then exhibit its action through the medium of RNA thus synthesized.