Iron (Fe) is one of the key nutrients transported by the placenta during gestation, required for many biological processes. Iron deficiency is disturbingly common and is even more prevalent in pregnant women, as the requirements for Fe increase due to the demands of the growing baby. Iron is absorbed mainly through the duodenum and is stored in the liver until required. We have shown, using dietary approaches, that the fetus accumulates Fe at the expense of the mother, maintaining normal iron levels even when she is seriously anaemic, but how this is accomplished is not well understood. The fetal requirements for Fe are regulated through the fetal liver and the placenta, and in this presentation, we demonstrate a model that we are using to investigate how the interaction takes place. The model may also be of value to others investigating the interactions between the fetal liver and the placenta. The approach involves co-culturing BeWo (b30 subclone) cells with HepG2 cells. The BeWo cells are grown on polycarbonate 0.4 μm pore inserts with HepG2 cells on the plate itself. The HepG2 cells on the base represent fetal liver cells and the basolateral side of the placenta while the compartment on top of the b30 cells represents the apical side of the placenta. The cells were cultured together for 7 days and during this time the transepithelial resistance (TEER) of the b30 cells was measured daily. During this time, TEER levels increased to about 175 ± 3 Ω (n= 7). There was no significant difference between plates with or without HepG2 cells in the basal layer At day 7, ⁵⁹Fe-Tf (1 μM, 0.5 μCi.ml^-1) was added to the apical side of the placental cells. At increasing time intervals up to 8 h, 0.25 mL aliquots were removed from the basolateral medium, and were replaced by new medium. The aliquots removed were counted for the appearance of ⁵⁹Fe. Active transport was demonstrated by comparing the differences between cells incubated at 4 ^oC and 37 ^oC. Transfer of ⁵⁹Fe across the BeWo cell layer was markedly greater in plates grown without HepG2 cells (3.86 ± 0.6 pmol/min/filter) than those with (1.56 ± 0.19 pmol/min/filter, p = 0.004, n = 6). The difference could not be accounted for by accumulation of ⁵⁹Fe in the HepG2 cells but suggest that the presence of the liver cells in the basal layer inhibits the uptake and transfer of ⁵⁹Fe by the BeWo cells. At this stage, there are many possible explanations, but we are testing the hypothesis that the liver cells signal their normal iron status, to the placental cells, and are indicating a reduced Fe requirement. This is a very exciting possibility, since, if correct, it suggests that we can study liver and placental interactions in vitro in a model which is relatively easy to manipulate when compared to in vivo studies in animals. Acknowledgements: This work was supported by SEERAD and the EU (FOOD-CT-2005-007036)