Isolated rat hepatocytes accumulate iron from iron-transferrin by a process which is dependent on the temperature and on the transferrin concentration, and which is diminished by treatment of the cells with a proteolytic enzyme. These observations are consistent with a mechanism for iron uptake into hepatocytes involving the binding of iron-transferrin to a specific cell-surface receptor. Apotransferrin is also able to bind to the hepatocyte but the apparent binding constant is about 35 times lower than that observed for the binding of iron-transferrin. The binding of apotransferrin to the cells is completely abolished by a low concentration of iron-transferrin. This suggests that the apotransferrin is binding weakly to the same receptor to which iron-transferrin binds and that there are not receptors on the surface of the hepatocyte specific for apotransferrin. In the absence of such specific-binding sites, apotransferrin may act as a passive acceptor of iron released from the hepatocyte.