Neuregulins have several important functions in the development of the peripheral nervous system, acting on both developing Schwann cells and muscle fibers. To determine whether these factors are also important for peripheral nerve regeneration, we have analyzed neuregulin expression in motor and sensory neurons by Northern blots and in situ hybridization. The results of this analysis show that the predominant neuregulin isoform expressed in these neurons is a novel transmembrane splice variant. After axotomy, there is a rapid decline in neuregulin expression in both motor and sensory neurons, but following reinnervation of target tissues, neuregulin expression returns to near normal levels. These results indicate that the normal expression of neuregulins in these neurons is maintained by the interactions with target tissues.