The HFE protein, which is defective in hereditary hemo-chromatosis, normally is expressed in crypt enterocytes of the duodenum where it has a unique, predominantly intracellular localization. In placenta, the HFE protein co-localizes with and forms a stable association with the transferrin receptor (TfR), providing a link between the HFE protein and iron transport. Immunocytochemistry shows that the HFE protein and TfR both are expressed in the crypt enterocytes. Western blots show that, as is the case in human placenta, the HFE protein in crypt enterocytes is physically associated with the TfR and with β2-microglobulin.