Little is known about the neurotrophic factors that may regulate maintenance, growth, and/or repair of corticospinal motor neurons (CSMN) in the developing or the adult mammal. We have developed an adult rat in vivo model of CSMN injury involving (i) bilateral prelabeling of CSMN with a cervical spinal cord injection of cholera toxin B subunit (CTB), (ii) unilateral axotomy close to the cell bodies by an intracortical lesion between cell layer V and the corpus callosum, and (iii) implantation of a continuous infusion device in the cortical parenchyma near the lesion. Two weeks later, coronal sections of the cortex are immunostained for CTB, and CTB-stained neurons are counted over defined section areas and compared to those on the contralateral (nonlesioned, noninfused) side. CTB-stainable neurons were 30-40% of the control side when the lesion was about 200 microns from the deeper face of the cell layer, and survival increased with increasing lesion depths. The model can be used to assess protective effects of potential CSMN trophic factors. The low survival achieved with the more superficial lesions (200 and 300 microns) was markedly improved by continuous infusion of ciliary neurotrophic factor at 0.1 to 1.0 microgram/day.