The maternal leukocytes present in human decidua during the early weeks of pregnancy are composed of CD56+ NK cells (approximately 80%), CD3+ T cells (approximately 10%), and CD14+ macrophages (approximately 10%). These leukocytes are present in large numbers at the implantation site where trophoblast invades. The migrating extravillous trophoblast (EVT) cells express HLA class I antigens HLA-G and HLA-C. To examine whether EVT or other allogeneic cells are capable of inducing a local proliferative response in maternal decidual leukocytes, we have assayed [3H]thymidine incorporation by decidual leukocytes co-cultured with irradiated trophoblast or peripheral blood lymphocytes (PBL). No proliferative response was seen in decidual leukocytes either to trophoblast or to PBL as stimulators. In addition trophoblast did not stimulate a proliferative response in PBL. These findings indicate that extravillous trophoblast is not capable of initiating a classical immune response at the implantation site.