The process of implantation, necessary for all viviparous birth, consists of tightly regulated events, including apposition of the blastocyst, attachment to the uterine lumen, and differentiation of the uterine stroma. In rodents and primates the uterine stroma undergoes a process called decidualization. Decidualization, the process by which the uterine endometrial stroma proliferates and differentiates into large epithelioid decidual cells, is critical to the establishment of fetal-maternal communication and the progression of implantation. The role of bone morphogenetic protein 2 (Bmp2) in regulating the transformation of the uterine stroma during embryo implantation in the mouse was investigated by the conditional ablation of Bmp2 in the uterus using the (PR-cre) mouse. In rodents and primates the process of implantation consists of attachment and invasion of the uterine luminal epithelium. Successful embryo implantation in these species requires the rapid remodeling of the uterine stromal cells in a process termed decidualization (as reviewed previously [30]). Decidualization is a process characterized by morphological and functional changes in the uterine stromal cells that is characterized by endometrial stroma proliferation and differentiation into large epithelioid decidual cells. This process is critical for establishment of a fetal-maternal interface during implantation. Although the expression of many genes, including steroid hormone receptors, cytokines, growth factors, and several developmental factors, has been implicated in this process, direct in vivo evidence of gene function has been limited. This is largely due to the fact that the ablation of many of the genes implicated in this process result in early lethality or other developmental consequences that preclude further study. Here we investigate the role of a member of the bone morphogenetic protein family, Bmp2, in the process of embryo implantation.Bone morphogenetic proteins (Bmps) are multifunctional growth factors that belong to the transforming growth factor  (TGF-) superfamily. The roles of Bmps in embryonic development and cellular functions in postnatal and adult animals have been extensively studied in recent years. The activity of Bmp growth factors was first described in the induction of bone formation (56). Bmp2 was identified later as a soluble factor capable of inducing ectopic cartilage and bone formation in vivo when implanted into muscular tissues (58, 61). Numerous studies have characterized the role of Bmp2 as an essential osteoblast and osteoclast differentiation factor (reviewed in reference 5). Mice with a targeted deletion of Bmp2 are embryonic lethal due to a failure of proamniotic canal closure in the majority of mice or abnormal cardiac development in the surviving mice (67). In the uterus of pregnant mice, Bmp2 expression is absent in the preimplantation period and during implantation is initially detected in the stroma surrounding the site of blastocyst attachment. As implantation progresses, expression of Bmp2 ...