Northern blotting, in situ hybridization and immunocytochemistry were used to study the changes in levels of mRNA coding for peripherin and in immunoreactivity of peripherin, a type III neuronal intermediate filament, in rat spinal motor neurons following axotomy of the sciatic nerve. For comparison, parallel studies examined the biology of neurofilament (NF) proteins in this model. The sciatic nerve was crushed at the junction of the L4-L5 spinal nerves. Levels of messenger RNA (mRNA) coding for peripherin in the motor neurons doubled by 4 days postaxotomy and remained elevated for a period of 6 weeks. Within 4-7 days of injury peripherin immunoreactivity increased significantly in cell bodies of motor neurons and remained elevated through 6 weeks. In contrast, no changes were detected in NF-M immunoreactivity over the same time period. By 8 weeks postaxotomy, levels of peripherin mRNA and protein returned to control values. The increases in the expression of peripherin parallel those of beta-tubulin and actin, and these changes are quite different from the alterations in neurofilament mRNA that decrease after axotomy. The contrasting responses of peripherin and NF to nerve injury indicates that each of these intermediate filaments may play distinct roles in nerve growth and regeneration.