Previous behavioral, electrophysiological, pharmacological, and genetic studies of mutations of the para locus in Drosophila melanogaster suggested that these mutations alter the structure or function of sodium channels. To identify the protein encoded by this gene and to elucidate the molecular basis of the mutant phenotypes, genomic DNA from the para locus was cloned. Mutational lesions in nine different para alleles were mapped and found to be distributed over a region of 45 kb. Analysis of cDNAs revealed that the para locus comprises a minimum of 26 exons distributed over more than 60 kb of genomic DNA. The nucleotide sequence of the complementary DNA predicts a protein whose structure and amino acid sequence are extremely similar to those of vertebrate sodium channels. The results support the conclusion that para encodes a functionally predominant class of sodium channels in Drosophila neurons. Furthermore, the para transcript appears to undergo alternative splicing to produce several distinct subtypes of this channel.