Beginning with the unexpected finding by cDNA array analysis that neuropilin-2 is induced in sciatic nerve distal to a transection, we document, for the first time, up-regulation in the axotomized adult peripheral nervous system of class 3 semaphorins and their receptors, which are known to play prominent roles in axonal guidance during neural development. Previously, we described the use of cDNA arrays to screen for novel peripheral nervous system axotomy-induced candidate neurotrophic proteins. A novel finding of that prior study was substantial induction of neuropilin 2 (NP2) mRNA in the axotomized nerve segments. Following up on that initial observation, we have now used real-time quantitative reverse transcription-polymerase chain reaction to demonstrate induction of genes encoding neuropilin 1 (NP1), which, like NP2, serves as a coreceptor for members of the class 3 semaphorin family of axonal guidance molecules and of five of the six known class 3 semaphorins (Sema3A, Sema3B, Sema3C, Sema3E, and Sema3F, but not Sema3D) in crushed or transected sciatic nerves.