Receptor-mediated endocytosis and recycling of transferrin is partly inhibited by the ferrous iron chelator bipyridine, which almost completely blocks iron uptake. Bipyridine causes iron release at the cell surface, but inhibition of iron uptake is also due to a blockage of its passage through the endosomal membrane. The rate of release of iron to bipyridine is decreased by the competing electron acceptor ferricyanide and by amiloride, but not by iron uptake inhibiting acidotropic amines. Transferrin reduction at the plasma membrane may be artificially induced by presence of a ferrous chelator and caused by low-affinity transmembrane NAD(P)H oxidoreductase.