In the rat, sciatic and saphenous nerve section resulted in self-mutilation of the ipsilateral limb. Fifteen and 60 days after surgery, monoamine levels were altered not only in the spinal cord but also in supraspinal structures. Thus, in the ipsi- and contralateral sides of the spinal lumbar region, an increase in the levels of 5-hydroxyindoleacetic acid (5-HIAA) was observed 15 days after surgery and in the levels of serotonin (5-HT) and noradrenaline 60 days later. Changes in the content of 5-HT and its metabolite were also evident, at these time points, in periaqueductal gray matter and trigeminal nucleus. Chemical sympathectomy carried out by administering guanethidine to neonatal rats reduced the degree of autotomy and suppressed the changes in monoaminergic systems following peripheral neurectomy. This study supports the hypothesis that the local noradrenaline outflow from sympathetic fibers in the neuroma is one of the causal factors in autotomy and it indicates that autotomy is under the control of descending monoaminergic pathways originating in brain-stem nuclei.