Monoclonal and polyclonal antibodies were generated against the voltage-dependent sodium channel purified from rat brain, and were used to characterize and localize sodium channels within mammalian central nervous system (CNS) and peripheral nervous system (PNS). These antibodies immunoblot and immunoprecipitate from labeled membrane proteins a 260-kDa polypeptide, as well as immunoprecipitate sodium channels saturated with [3H]saxitoxin. These monoclonal and polyclonal antibodies do not, however, recognize sodium channels in cardiac or skeletal muscle. Immunocytochemical analyses of cultured CNS and PNS neurons and immuno-ultrastructural localization of sodium channel reactivity within CNS tissue in situ indicate that these probes provide a unique tool for studying the level of expression, organization and turnover of sodium channels within the CNS and PNS.