An important chapter in neuroscience was opened up by Tom Sears and his colleagues (see e.g. Rasminsky & Sears, 1972; Bostock & Sears, 1976, 1978) when they carried out their beautiful analyses, using the external longitudinal current recording method, of nodal and internodal transmembrane currents in myelinated and demyelinated ventral root fibres, by implication beginning to define the molecular anatomy of the node of Ranvier. Since that time, the sequestration of voltage-sensitive Na+ channels in the axon membrane at the node has been further examined using a variety of techniques including saxitoxin-binding (Ritchie & Rogart, 1977), cytochemical methods (Quick & Waxman, 1977a), freeze-fracture (Rosenbluth, 1976), immuno-electron microscopy (Black et al., 1989), nodal voltage clamp (Chiu & Ritchie, 1981, 1982; Neumcke & Stämpfli, 1982) and single channel patch clamp (Vogel & Schwarz, 1995); and the expression of various types of K+ channels in myelinated axons has been studied using electrophysiological and pharmacological methods (Waxman & Ritchie, 1993; Vogel & Schwarz, 1994). This chapter will discuss some of the newer aspects of the molecular anatomy of the mammalian node of Ranvier, with emphasis on Na+ channels, the Na+–Ca2+ exchanger, and the diffusion barrier that accumulates intra-axonal Na+ in a limited space below the axon membrane.