The effect of unilateral transection of the sciatic nerve on expression of immunoreactive galanin (GAL), galanin-message-associated peptide (GMAP) and neuropeptide tyrosine (NPY) in dorsal root ganglia (DRGs) was studied in wild-type mice and in leukemia inhibitory factor (LIF)-deficient mice. In normal and contralateral DRGs small numbers of weakly fluorescent GAL- and GMAP-positive neuronal cell bodies and numerous positive fibers were observed. No NPY-positive cell bodies but a few fibers surrounding blood vessels were seen. In LIF deficient mice hardly any GAL- or GMAP-positive neurons or fibers were seen, nor was NPY-like immunoreactivity present in cell bodies. After axotomy there was a dramatic upregulation of all three peptides in wild-type DRG neurons, whereby 50-60% of the neuron profiles, encompassing both small and large profiles, were GAL- and GMAP-immunoreactive (IR). About one third of all neuron profiles, mainly large ones, were NPY-positive. In LIF-deficient mice this upregulation was much less pronounced. Thus GAL- and GMAP-IR neuron profiles were reduced by 65-70% compared with the wild-type mice. The number of NPY-positive neuron profiles was reduced to half but this difference was not significant. There was also an ipsilateral decrease in fluorescence intensity for all three peptide immunoreactivities in the LIF-deficient mice as compared with wild-type mice after axotomy. There was no apparent difference in size between, respectively, GAL- and GMAP-positive profiles when comparing LIF-deficient and wild-type mice before or after axotomy. There were, however, no small NPY-IR profiles in the LIF-deficient group. The present results suggests that LIF is important for the dramatic upregulation of GAL and GMAP seen after axotomy. It may also be important for the normal expression of galanin in mouse DRGs, since wild-type mice seemed to have somewhat more positive cell bodies and more fluorescent fibers. LIF seems to be less important for the control of NPY synthesis, but may be involved in NPY regulation in small-sized neurons.