Neuropeptides have long been considered to act as neurotransmitters or neuromodulators, but they may also contribute to a variety of regulatory and trophic neuronal functions. In the present study, we determined the effects of axotomy on the levels of the neuropeptide calcitonin gene-related peptide (CGRP) in trochlear motoneurons (TMNs) of adult cats. The number of neurons with detectable CGRP immunoreactivity, and the intensity of their CGRP immunoreactivity, increased dramatically 1 week postaxotomy, gradually returned toward normal levels, but remained significantly higher than normal 12 weeks postaxotomy--a time when axonal regeneration and functional reinnervation of the superior oblique muscle should be complete. Our observation that CGRP levels in TMNs increase after axotomy suggests a role for this peptide in the response of motoneurons to injury and in regeneration. In addition, since many axotomized TMNs die, we suggest that the maintenance of high CGRP levels even after regeneration is complete may reflect an increased load on those TMNs that survive.