Expression of the nerve growth factor receptor (NGF-R) mRNA in adult motor neurons is increased by axonal injury. The present study was designed to examine, by immunocytochemistry, the onset, course, and specificity of NGF-R up-regulation following distal or proximal crush of the sciatic nerve. Lesions at both levels induced the appearance of NGF-R-like immunoreactivity in motor neurons beginning on day two postaxotomy. NGF-R-like immunoreactivity was present exclusively in axotomized neurons, as verified by the near complete colocalization of immunoreactive NGF-R with a fluorescent retrograde tracer injected at the crush site. NGF-R expression was closely linked with disconnection of cells from the target; one week after muscle reinnervation, NGF-R immunoreactivity was no longer detectable in animals with distal injuries. These results extend the previous findings of axotomy-induced expression of NGF-R mRNA to the level of the receptor. Furthermore, our observations are consistent with the hypothesis that target-derived factors participate in the regulation of NGF-R gene expression in adult motor neurons.