Despite genetic differences, mothers do not reject their semiallogeneic embryos. Regulated expression of the major histocompatibility antigens (HLA) by placental trophoblast cells, which intervene between the embryo and maternal blood and tissues, is now believed to play an important role in this surprising feature of pregnancy. Transcription and translation of the highly polymorphic class I HLA-A, -B, -C genes whose products stimulate graft rejection are blocked in trophoblast cells. Instead, these cells express HLA- G, a nonpolymorphic gene. Moreover, the cells do not express class II HLA-D antigens, and factors such as interferons that usually enhance HLA expression have no effect on trophoblast cells in situ. Thus, multiple regulatory mechanisms prevent the cells that sequester the embryo from the mother from expressing the potentially deleterious paternal HLA antigens, immunological rejection is avoided and successful pregnancy ensues.