It is known that, under stress conditions the hypothalamo-pituitary-adrenal (HPA) axis is stimulated and catecholamine production is increased. Adrenomedullin (ADM) is a novel peptide that elicits a long-vasorelaxation, and participates in blood pressure regulation via different mechanisms. In the present study, we investigated the administration of ADM on tyrosine hydroxylase (TH) enzyme activity in cold exposed rats. Four groups of Sprague-Dawley rats were studied for their TH enzyme activity in the adrenal medulla and hypothalamus. In addition to measuring blood pressure in these rats, TH enzyme activity in both the adrenal medulla and hypothalamus were examined in four groups of Sprague-Dawley rats: animals exposed to room temperature and cold stress (8degreesC, 48 h), and rats injected with ADM (1.0 nmol/kg, i.v.) alone and/or together with cold stress. TH activity was shown to be increased in cold treated groups and decreased in ADM and ADM + cold stress group. Our findings appear to suggest that external ADM application caused an opposite effect on the same system in rats, decreasing the activity of tyrosine hydroxylase (TH) enzyme activity. Furthermore, externally applied ADM was shown to produce its expected hypotensive effect in cold-stressed rats. Our results suggest that a possible explanation for the effects of ADM is that, the uptake of ADM under cold stress may effect TH activity in studied tissues.