To initiate the establishment of an epitheliochorial placenta, the developing porcine conceptuses contact the maternal endometrium on its mesometrial side. The porcine conceptuses secrete estrogens which, together with circulating maternal hormones, govern variations in the structure as well as expression and levels of steroid receptors and growth factors during early pregnancy. Mesometrial samples of endometrium or placenta were collected from 15 early pregnant (8-30 days after the onset of estrus) and six cycling (days 1-14) gilts. The variations in tissue morphology and immunohistochemical localization of insulin-like growth factor-I (IGF-I) were related to the tissue levels (by enzyme immunoassay) of receptors for estrogen (ER) and progesterone (PR), as well as mRNA (by solution hybridization) concentrations for the two receptors and IGF-I. IGF-I immunoreactivity was present in samples from all animals, being principally located in maternal epithelium, trophoblast, endothelium and vascular smooth muscle; the latter showing the strongest labeling. The levels of receptor proteins, as well as mRNAs, were highest in the non-pregnant animals at estrus and metestrus. The pregnant animals showed decreasing concentrations to consistently low levels after day 14. Temporal changes in the studied parameters were clearly coincidental with the peak (days 13-14) in conceptus estrogen secretion, e.g. the more uniform IGF-I immunolabeling in the uterine glands (days 8-13) compared with the later stages studied; the conspicuous accumulation and release of secretory vesicles in the endometrial glands (days 8-13), marking the change in secretory quality and quantity, leading to a gradual shift from histotrophic to hemotrophic nutrition of the conceptuses, and finally, the peaking level of IGF-I mRNA in the pregnant endometrium (days 12-13) which decreased considerably thereafter. It is concluded that IGF-I activity in the porcine uterus changes with the early development of the placenta.