We have characterized and sequenced cDNA clones corresponding to the neural-specific SCG10 mRNA. The predicted amino acid sequence is novel and not strongly homologous to that of any known polypeptide. The protein is encoded by two mRNAs that differ in their choice of polyadenylation site. Immunocytochemical localization experiments using an affinity-purified antibody (against an SCG10-TrpE fusion protein) reveal accumulations of punctate staining in the perinuclear cytoplasm, axons, and growth cones of cultured neurons. SCG10 levels are maximal in the embryonic CNS but are dramatically reduced in the adult. Preliminary cell fractionation experiments suggest that the protein is tightly associated with membranes but is not itself an integral membrane protein. The apparent localization and timing of expression of the SCG10 protein are reminiscent of GAP-43, but the sequences of the two polypeptides are unrelated. Cross-hybridizing mRNAs and antigenically related proteins are found in several nonneuronal cell lines that do not express SCG10.