A morphometric and scanning electron microscopic analysis of endometrial, luminal topographical changes of cyclic and ovariectomized, ovarian steroid-treated guinea pigs was undertaken to determine the effects of cyclic endocrine influences on the uterine surface features recognized to be involved in the process of interstitial blastocyst implantation. Estrogenic stimulation of the uterine epithelial layer induced microvillus growth and closed the endometrial gland openings on the luminal surface. Progestins antagonized these parameters, as indicated by short, sparse microvillus formation over a flat luminal uterine surface on which gland openings were both numerous and prominent. The combined effects of estrogen and progesterone therapies induced luminal epithelial changes resembling those characterizing the cyclic uterine surface at the time of blastocyst implantation. These data indicate that the cyclic alterations in the uterine luminal surface are directly regulated by ovarian steroid hormones, and that these changes in surface structure are synchronized and directly involved in the preparation for blastocyst-uterine interaction during the nidatory process in this species. Anat. Rec. 252:205-214, 1998. 1998 Key words: uterus; scanning electron microscopy; guinea pig; estrogens; progestins Scanning electron microscopy (SEM) has been used to study the luminal surface morphology of the oviduct (Dirksen and Satir 1972;Ferenczy et al., 1972;Kanagawa et al., 1972;Ludwig et al., 1972; Patek et al., 1972a,b;Dirksen, 1974;Rumery and Eddy, 1974), uterus (Psychoyos and Mandon,1971;Hafez, 1972Hafez, , 1973 Johnnisson and Nilsson, 1972;Anderson et al., 1975;Jones and Hamer, 1975;Ferenczy, 1974Ferenczy, ,1976Motta and Andrews, 1976;Garris, 1984d), and vagina (Kanagawa et al., 1972;Parakkal, 1974) in a number of species, including human (Ludwig et al., 1972, at various stages of the reproductive cycle. Cyclic changes in the rat uterine surface structure are recognized to be under ovarian steroid hormone control (Anderson et al., 1975). While estrogens potentiate microvillus formation by increasing both the number and length of each cell process, progesterone is recognized to induce a diminution in the density and length of uterine epithelial microvilli. As a result, the apical cell surface and intercellular borders of the epithelial cells are more pronounced under the influence of progestins than estrogens. However, the short cycle length and the lack of a functional corpus luteum following ovulation in the rat does not allow for the evaluation of the uterine luminal surface changes which occur as a result of estrogen and progesterone interaction during the prolonged luteal phase of the reproductive cycle.