Vitamin E has been linked to fertility since its discovery in 1922. However, the exact mechanism by which alpha-tocopherol allows pregnancy to continue until term has remained puzzling over the last 80 years. Alpha-tocopherol transfer protein (TTPA) is expressed in liver and in Purkinje cells of the cerebellum. TTPA is suggested to be responsible for the transfer of alpha-tocopherol across barrier membranes. Ttpa-knockout mice are infertile and show symptoms similar to those observed in severe vitamin E deficiency. We thus investigated TTPA expression in human placenta and whether clues from its localization in different parts of the placenta might be of functional significance. TTPA-mRNA transcripts were quantified with a fluorescent 5'-nuclease assay (TaqMan) in five different tissues. Placental expression ranged second behind that of liver. Immunohistochemistry identified TTPA in the cytosol but also in nuclei of the trophoblast and in the endothelium of the fetal capillaries. Expression in trophoblast and fetal capillaries' endothelium indicates a role of TTPA in the stereoselective transport of RRR-alpha-tocopherol from the maternal to the fetal plasma. In amnion epithelial cells, however, TTPA was predominantly located in the nuclei. Nuclear localization of the protein may represent a novel function of TTPA.