During in situ recovery from a lesion to the cerebrobuccal connective (CBC) in the snail Achatina fulica, neurons of the buccal ganglia undergo extensive regeneration and sprouting as assessed by axonal dye-fillings of the CBC. 2. These changes are preceded by the distal degeneration of severed fibres from the serotonergic metacerebral giant neuron (MCG), which results in the depletion of serotonin (5-HT) in the ipsilateral buccal ganglion. We have investigated the potential role of this depletion in causing some of the ensuing neuroplastic events. 3. Pharmacological depletion of 5-HT using either 5,7-dihydroxtryptamine or p-chlorophenylalanine in normal, unlesioned animals was found to produce supernumerary neuronal labelling similar to that seen following a lesion. 4. Systemic daily injections of 5-HT were found to partly suppress the sprouting response following the CBC lesion. For example, the contralateral, uninjured MCG which is normally induced by the lesion to sprout novel projections into the denervated ganglion, is suppressed from doing so by the 5-HT treatment. 5. These growth inhibiting effects of 5-HT upon the contralateral MCG could be antagonized by the prior administration of the 5-HT receptor blocker cyproheptadine, suggesting a specific receptor mediated action. 6. We suggest that 5-HT may play a role in governing the state of neuronal outgrowth in vivo in the CNS of the adult snail, as has been suggested by early development and neuronal cultural studies.