The placenta is a unique mixture of histoincompatible cells derived from mother and fetus. The aim of the present study was to obtain information on the development of macrophage subpopulations and reticulum cells during pregnancy in the placenta. Placentas of Wistar rats were removed at several stages of gestation, and were studied by immunohistochemical techniques applying monoclonal antibodies against macrophage subpopulations, lymphoid cells and reticulum cells. The expression of MHC class-II antigens was also studied. Throughout gestation macrophages were demonstrable in large numbers in the endometrium, in the myometrium and in the metrial gland, which is a compartment developing in the myometrium of pregnant rodents. In the labyrinth, a placenta compartment consisting of fetal cells, macrophages (probably of fetal origin) were already found on day 15. In the spongiotrophoblast and decidua basalis, which are layers of the placenta containing both maternal and fetal cells, only a few macrophages were recognized throughout gestation. The monoclonal antibody ED11, raised against reticulum cells, recognized fiber-like structures lining the blood sinuses of the spongiotrophoblast, in which only maternal blood is circulating. As the antigen recognized by ED11 is believed to play a role in the trapping of immune complexes, the spongiotrophoblast may play a role in the protection of the fetus from circulating immune complexes.