The intersegmental nerve (ISN) of the Drosophila embryo follows a reproducible course near the anterior border of each segment. Based on the experiments reported here, we suggest that growth of the axons constituting the nerve is guided, in part, by the transmembrane proteins Delta and Notch. In particular, we suggest that expression of Delta protein on a branch of the trachea provides a path for the nerve through the lateral part of the embryo, and that the growing axons use the Notch protein on their surfaces to recognize this path. Consistent with this idea, we show that disruption of the trachea abolishes the ability of the ISN to extend through this part of the embryonic periphery. Finally, we argue that the same regulatory network that directs these peripheral axons also specifies the trajectory of part of the axonal scaffold of the central nervous system.