In this study, we have investigated the effect of fibroblast growth factors (bFGF and FGF-5) and brain derived neurotrophic factor (BDNF) on the expression of calcitonin gene-related peptide (CGRP) in rat motoneurons in vivo and in vitro. Following sciatic nerve transection in adult rats, the levels of alpha-CGRP and beta-CGRP mRNA were up- and down-regulated respectively in axotomized motoneurons, revealed by in situ hybridization histochemistry. Local administration of 1 microgram bFGF was able to entirely abolish the up-regulation of alpha-CGRP mRNA, and to further down-regulate beta-CGRP. These effects, albeit less pronounced, were still evident with 0.2 micrograms bFGF. In contrast, bFGF did not attenuate the lesion-induced decrease of choline acetyltransferase (ChAT) mRNA. Administration of BDNF did not significantly alter the expression of CGRP or ChAT mRNA in axotomized motoneurons. Both alpha- and beta-CGRP mRNAs could be detected by PCR in enriched motoneuron cultures prepared from rat embryos at embryonic day 14-15. Comparing the amplification of alpha- and beta-CGRP mRNAs with that of mRNA encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in parallel samples, we found that cultures treated with FGF-5 had a lower ratio of alpha- and beta-CGRP mRNA to GAPDH mRNA, than did control or BDNF-treated cultures. BDNF, on the other hand increased alpha-CGRP and decreased beta-CGRP mRNA levels, though these effects were moderate compared with the effects of FGF-5. The results obtained in this study suggest that members of the FGF family of growth factors influence the expression of CGRP in rat motoneurons, and that the increase of this neuropeptide induced by axotomy may, at least in part, be due to deprivation of these target-derived factors.