GAP-43 is a gene expressed only in the nervous system. The protein product is believed to be important to neuronal growth and plasticity. Most, and likely all, neurons express high levels of GAP-43 during periods of neurite elongation. To initiate studies of GAP-43 gene regulation we have cloned the rat gene encoding GAP-43. The GAP-43 gene includes three exons. The first exon encodes only the amino terminal 10 amino acids, which corresponds to the membrane targeting domain of GAP-43. The second exon encodes a putative calmodulin binding domain and a protein kinase C phosphorylation site. The 5'-flanking sequence is unusual in that it lacks CAAT or TATA elements, and directs RNA transcription initiation from several sites. Some of the transcription start sites are used to a different degree in the central and peripheral nervous systems.