In this study we have analysed, by in situ hybridization, the expression of the genes for both alpha-CGRP and beta-CGRP in hypoglossal motor nuclei following transection of the left hypoglossal nerve. Our results show that the gene for alpha-CGRP displays a peculiar sequence of regulation (a successive up-down-up-recovery sequence) within ipsilateral hypoglossal motoneurons in response to axotomy. It is initially up-regulated, then down-regulated (displaying mRNA levels below basal), and later again up-regulated before recovery. By contrast, the gene for beta-CGRP displays a successive and distinct up-down-recovery sequence of regulation (it does not display a second increase in mRNA production). The first up-regulation of the alpha-CGRP gene occurs just during the early period of perineuronal glial reaction and the second up-regulation just during the period of delayed astrocyte reaction and muscle reinnervation. Because alpha-CGRP is a neuron-derived factor for many types of cells, including astrocytes and skeletal myocytes, our results suggest that the pleiotropic alpha-CGRP may be a motoneuron-derived trophic signal for both glial and skeletal muscle cells in order to maintain the motoneuron itself and, in consequence, might be of therapeutic interest in treating degenerative disease of motoneurons. beta-CGRP might be redundant within the hypoglossal motoneurons.