Transfer of maternal IgG through the human placenta furnishes the newborn with passive immunity to a number of infectious agents. The exact mechanism of this transfer is still unknown, but it is agreed that it involves active receptor-mediated transport. The neonatal Fc receptor is a major histocompatibility complex class I-like receptor originally identified in the intestines of newborn rodents. A similar receptor has recently been detected in human placental syncytiotrophoblasts. Using multilabeling fluorescence immunohistochemistry and confocal laser scanning microscopy, we found that the neonatal Fc receptor co-localizes with IgG and beta 2-microglobulin in granules of human placental syncytiotrophoblast. The Fc receptor is not detected on syncytiotrophoblast apical plasma membrane. Localization to the outermost cellular barrier between the fetal and maternal blood further strengthens the role of the Fc receptor in transplacental transport of IgG.