The aim of our study was to investigate the effect of extended (48 h) cold (8 degrees C) exposure on oxidative stress and antioxidant defense system in hypothalamus and adrenal medulla, which are both key components of the hypothalamic-pituitary-adrenal (HPA) axis. Male albino Spraque-Dawley rats were randomly divided into two groups-the control group (n = 12) and the cold stress group (n = 12). Tissue superoxide dismutase (SOD), catalase (CAT), glutathion S-transferase (GST) and glutathion reductase (GR) activities and glutathion (GSH) were measured using chemical protocols. In cold stress groups CAT activities were significantly increased in adrenal medulla and hypothalamus of rats; however, SOD activities were decreased in both tissues. Sub-acute cold exposure resulted in a significant increase in GR activity while GST was decrease in both tissues studied. The amount of GSH was also enhanced in adrenal medulla and hypothalamus of cold-stressed rats when compared to controls. Extended exposure of cold caused synergic changes in the hypothalamic and adrenal medullary antioxidative enzyme activities. This results lead us to conclude that cold stress can disrupt the balance in an oxidant/antioxidant system and cause oxidative damage to HPA axis organs by altering the enzymatic and non-enzymatic antioxidant status. (c) 2006 Elsevier Ltd. All rights reserved.