We found an increase in calcitonin gene-related peptide (CGRP)-like immunoreactivity in motoneurons of rat spinal cord after peripheral axotomy. By means of in situ hybridization histochemistry and Northern blotting, we further demonstrated that this increase was the result of increased levels of alpha-CGRP mRNA, not beta-CGRP mRNA. The increased level of alpha-CGRP mRNA was maintained for at least 5 weeks, and was present on both sides. In addition, alpha-CGRP and beta-CGRP mRNAs had different distributions from each other in the dorsal root ganglia and levels of both were decreased after axotomy. These results indicate that alpha-CGRP and beta-CGRP are regulated independently and have different roles in the motor and sensory systems of the spinal cord.