Care et al. report that macrophages have a central role in early pregnancy in mice. The deletion of CD11b+ cells early after conception led to defective embryo implantation, whereas the administration of macrophages rescued this phenotype. For implantation to occur, the endometrium undergoes structural changes in response to progesterone. Progesterone is secreted by the corpora lutea, which develop from ovarian follicles following ovulation. Macrophage depletion disturbed the luteal microvasculature and lowered the levels of progesterone in the blood, whereas progesterone treatment restored the capacity for pregnancy in CD11b+ cell-depleted mice. These and other findings suggest that the pro-angiogenic and, possibly, the anti-inflammatory functions of macrophages sustain the development and the function of the corpora lutea in early pregnancy.