Mutations in the unc-51 gene of the nematode Caenorhabditis elegans result in various abnormalities in axonal elongation and axonal structures. We cloned the unc-51 gene by tagging with the transposon Tc1. The wild-type unc-51 gene, which rescued the mutant phenotypes, encodes a novel serine/threonine kinase of 856 amino acids. Mutation sites were identified in the unc-51 gene of six mutants. A Lys-->Met mutation created in vitro in the kinase domain led to the loss of rescuing activity and was dominant negative, indicating that the kinase domain of Unc-51 is essential for the function. Expression of an unc-51/lacZ fusion gene was observed in many neurons at all stages. We propose that protein phosphorylation by the unc-51 product is important for axonal elongation and possibly for axonal guidance.