During development, neurons are capable of selecting specific pathways that lead them to their appropriate target areas. A variety of molecular mechanisms are thought to be involved in pathway recognition, including cell adhesion, repulsion and chemotropism. However, apart from a few genes whose involvement has been shown genetically, the mechanisms underlying neuronal pathway selection are largely unknown. Here we report the isolation of the Drosophila derailed (drl) gene, which encodes a novel member of the receptor protein-tyrosine kinase family. Using a newly developed axon-targeted reporter gene we find that drl is expressed by a small subset of embryonic interneurons whose growth cones choose common pathways during development. In drl mutant embryos these neurons fail to make the correct pathway choices. Our results provide evidence for receptor protein-tyrosine kinase involvement in key aspects of neuronal pathway recognition.