The effect of axotomy (3, 10 and 21 days) on the expression of some neuronal markers was analysed in dorsal root ganglia and spinal cord of guinea-pigs using immunohistochemistry. Three weeks following injury, substance P-like immunoreactivity (-LI) was slightly reduced in the DRGs of the ipsilateral side, whereas a marked increase in neuropeptide Y(NPY)-LI could be detected ipsilaterally and a smaller increase contralaterally. NPY-LI was mainly expressed in small, but also some medium-sized and large neuron profiles after axotomy. Galanin-LI showed a moderate bilateral increase. No significant changes could be observed in DRGs for calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide-, peptide histidine isoleucine- or nitric oxide synthase-LIs. In the ventral horn CGRP-LI was slightly increased bilaterally in motoneurons, most pronounced on the injured side. Autotomy behaviour was seen in seven of the nine animals in the twenty-one day group. The present results demonstrate that also in guinea-pigs several peptides undergo distinct changes in their expression after peripheral nerve injury. However, in contrast to rats and monkeys, galanin-LI is only moderately increased in guinea-pigs. Neuropeptide Y showed a dramatic increase mainly in small neurons, in contrast to the upregulation in large neurons in the rat. Thus, distinct species differences exist with regard to the cellular response to nerve injury.