Genetic elements involved in cell-specific expression of the type II sodium channel gene were revealed using transient expression assays. A chimeric reporter gene containing 1051 bp of the sodium channel 5' flanking region was active in neuroblastoma and PC12 cells, but inactive in nonneuronal cell types. Deletion of upstream sequences resulted in an 80-fold increase in reporter gene activity in skeletal muscle cells, suggesting the presence of negative elements. Although no homologies were found between sequences in the type II 5' flanking region and other negative elements or "silencers," a small region common to the type II gene and other genes expressed in the nervous system was identified and may be involved in transcriptional regulation of neuronal genes.