We investigated the effects of central and peripheral axotomy of the sensory neurons in the nodose ganglion on neurite outgrowth and neuropeptide expression. Axonal outgrowth was studied in ganglia subjected to a conditioning lesion of the vagus nerve 6 days prior to in vitro explantation. In such cultures, a conditioning effect, i.e. a shorter initial delay and faster axonal outgrowth, was observed after peripheral axotomy, while central axotomy had no effect. Neuropeptide expression was measured by immunocytochemistry 3 days after axotomy. Peripheral axotomy induced an increase in the number of neurons expressing the C-terminal flanking peptide of neuropeptide Y (C-PON), galanin (GAL) and vasoactive intestinal peptide (VIP). In contrast, central axotomy did not affect neuropeptide expression. These results suggest that both axonal outgrowth and expression of neuropeptides in the sensory neurons of the nodose ganglion could be regulated by the contact of the cells with their peripheral, but not their central targets.