Immunocytochemical localization of Na+ channel subtypes RI and RII showed that RI immunoreactivity is relatively low and homogeneous along the rostral-caudal extent of sagittal brain sections, whereas RII staining is heterogeneous and relatively dense in the forebrain, substantia nigra, hippocampus, and cerebellum. The somata of the dentate granule cells, hippocampal pyramidal cells, cerebellar Purkinje cells, and spinal motor neurons are immunoreactive for RI but not RII. In contrast, areas rich in unmyelinated nerve fibers, such as the mossy fibers of the dentate granule cells, the stratum radiatum and stratum oriens of the hippocampus, and the molecular layer of the cerebellum, are strongly immunoreactive for RII but not RI. Differential regulation of expression of RI and RII genes may allow differential modulation of Na+ channel density in somata and axons. The sites of RI localization correlate closely with sites where sustained Na+ currents have been recorded.