Clustering of voltage-gated Na+ channels is critical for the fast saltatory conduction of action potentials in vertebrate myelinated axons. However, the mechanisms responsible for the generation and maintenance of Na+ channel clustering are not well understood. In this study we have raised an antibody against the cloned SCAP-1 voltage-gated Na+ channel of the marine invertebrate Aplysia californica and used it to examine Na+ channel localization in Aplysia ganglia and in cultured Aplysia sensory neurons. Our results show that there is a large cytoplasmic pool of Na+ channels in the soma of Aplysia neurons. Furthermore, we show that Na+ channels in Aplysia axons are not homogeneously distributed but, rather, are present in distinct clusters. Theoretical considerations indicate that Na+ channel clustering may enhance action potential conduction. We propose that clustered Na+ channels may be a fundamental property of many axons, and perhaps of many membranes that conduct Na(+)-dependent action potentials.