The normal src protein (pp60c-src) is localized principally in the nerve growth cone of developing neurons and declines to low levels with synaptic maturation. To determine whether pp60c-src is reexpressed in regenerating axons, its expression was studied by immunoblotting and immunocytochemical analyses in adult chicken sciatic nerve following nerve crush injury. pp60c-src expression was found to increase during nerve repair with a temporal and spatial pattern consistent with a localization in regenerating axons. At the crush site, pp60c-src increased to maximal levels 7 days postinjury, increasing fivefold relative to 0 day nerve. In the nerve segment distal to the injury, the maximal increase in pp60c-src was sevenfold and occurred between 11 and 21 days postinjury. Immunoperoxidase staining revealed pp60c-src in regenerating axons and certain nonneuronal cells at the site of nerve repair. pp60c-src was induced in both motor and sensory neurons, as shown by increased pp60c-src immunoreactivity in their cell bodies located in the spinal cord and dorsal root ganglion. Phosphotyrosine-modified proteins that were potential targets of pp60c-src increased following nerve crush, and were localized to outgrowing neurites as well as to nonneuronal cells. These results suggest that pp60c-src is a common component of cellular mechanisms regulating growth cone migration in both regenerating and developing axons.