Transferrin (Tf) is thought to play a pivotal role in iron metabolism of various kinds of cells. Tf has specific receptors on the surface of the cells that require iron. Tf-receptor binding is followed by internalization through a system of coated pits and vesicles. The rapid decline of pH of these vesicles leads to the release and sequestration of iron by the cell. Apotransferrin-receptor complex returns to the cell surface, where under neutral pH conditions, apotransferrin is dissociated from the receptor. Recent advances in cellular and molecular biology, gene cloning and monoclonal antibody technique have elucidated many features of these processes at a molecular level. These advances are briefly reviewed, and particularly, our own observations concerning endothelial mediation of uptake of Tf by hepatocytes are discussed.