Abstract Monoclonal antibodies and alloantisera were used in an indirect immunohistochemical assay to determine the expression of class I and class II Major Histocompatibility Complex (MHC) antigens by equine placental cells and the endometrial tissues at the fetal-maternal interface. MHC class I antigens were expressed at high density on the surface of the trophoblast cells of the chorionic girdle at days 32–36, just prior to their invasion of the endometrium. The mature gonadotrophin-secreting cells of the endometrial cups, which are derived from the chorionic girdle cells, had greatly reduced levels of MHC class I antigen expression while no MHC class I antigens were detectable on the non-invasive trophoblast cells of the allantochorion, except in small isolated patches. MHC class I antigens inununo-precipitated from chorionic girdle cells with either monoclonal antibodies or alloantisera had a relative molecular mass of 44 000, which was identical to that of MHC class I antigens precipitated from lymphocytes with the same reagents. MHC class H antigens were not detected on any trophoblast cells, although they were expressed at high levels by the endometrial glandular and lumenal epithelium immediately bordering the endometrial cups. MHC class I antigens were also expressed at high levels by endometrial tissues in the area of the cups. The high level of MHC class I antigen expression by endometrial glands within and bordering the cups was in sharp contrast to the greatly reduced class I antigen expression by the mature endometrial cup cells themselves. Polymorphic, paternal, MHC class I antigens that are expressed by the invasive trophoblast cells of the chorionic girdle probably provide the antigenic signal for maternal anti-fetal alloantibody production in early horse pregnancy. Reduced expression of these antigens by terminally differentiated endometrial cup cells may represent a strategy for the protection of the conceptus from maternal immunological attack and destruction that is distinct from prevention of primary maternal sensitization.