The myelinated axon provides a model in which it is possible to examine how various types of ion channels are incorporated into a membrane to form an excitable neuronal process. The available evidence now indicates that mammalian myelinated fibers contain a repertoire of physiologically active membrane molecules including at least four types of ion channels and an electrogenic Na+,K(+)-pump. Physiological properties of myelinated fibers reflect the distribution of these various types of channels and pumps, as well as interactions with myelinating Schwann cells in the PNS or oligodendrocytes in the CNS. A growing body of data also suggests a role for astrocytes and Schwann cells at nodes of Ranvier. This article reviews the current understanding of the ion channel organization of the mammalian myelinated fiber.