Recent demonstrations of transferrin (TF) mRNA in placental tissue raised the possibility that the placenta may serve as an extra-hepatic source of this iron-binding protein during development. In this study, we first confirmed these findings using cRNA probes for TF, and then adapted the TF reverse haemolytic plaque assay for use with rat placental cells to identify the location and functional characteristics of cells secreting this product. We found TF releasing cells in placentae (day 19-21) with greater proportions present in cultures from basal than labyrinth zone regions. These cells appeared quite stable as evidenced by observations that fresh populations and 24, 48 and 72 h cultures from the same placental regions all contained similar percentages of secretors. The rate of TF plaque formation was greatly enhanced in the presence of tumour necrosis factor (0.1 ng/ml) for basal zone and yolk sac cells, but not for labyrinth zone cells, suggesting a potent but regionally specific modulation of TF release. When taken together, these findings demonstrate clearly that TF is released from cells of the placenta. Moreover, the regional differences in frequency and modulation of these cells suggests that the release of placental TF is a dynamic and carefully controlled process.