OBJECTIVE: The present study was designed to identify the acute and chronic immobilization stress-induced polyamine (putrescine) responses and their modulation by administration of melatonin in brain regions (frontal cortex and hippocampus) and gastrointestinal tract regions (GIT, gastric mucosa and duodenal mucosa). METHOD: For immobilization stress (3 or 14 days), rats (250-300 g, male Sprague-Dawley rats) were placed in restrainers once daily, for 3 h. Melatonin (10 mg/kg, i.p.) was administered once daily immediately after stress. Rats were sacrificed 2 h after the final application of stress for the measurement of putrescine levels. RESULTS: The putrescine levels of frontal cortex, hippocampus, gastric mucosa and duodenal mucosa were significantly increased by acute stress (p<0.05, p<0.05, p<0.0005 and p<0.01, respectively). The putrescine levels of frontal cortex and duodenal mucosa were significantly increased by chronic stress (p<0.05, respectively). In chronic stress group, animals showed adaptation tendency. The changes of putrescine level in gastric and duodenal mucosa induced by chronic stress were significantly lower than those by acute stress (p<0.05, respectively). The putrescine responses to acute stress in frontal cortex, hippocampus, gastric mucosa and duodenal mucosa were attenuated by administration of melatonin (p<0.01, p<0.05, p<0.05 and p<0.05, respectively). The putrescine response to chronic stress in frontal cortex was attenuated by melatonin administration (p<0.05, respectively). CONCLUSION: The results suggested that putrescine may play a role in stress response of brain regions (frontal cortex and hippocampus) and GIT regions (gastric and duodenal mucosa). Melatonin can inhibit the stress-induced putrescine responses in the brain and GIT.