Increased O2 consumption was found in rats after bilateral lesions of the lateral hypothalamus (LH) or during voluntary overeating. This phenomenon appears to be mediated by the sympathetic nervous system (SNS) in both conditions, since it is blocked by the beta-blocker propranolol administration. In the first experiment we showed that the brain cortex is involved in the thermogenesis induced by LH lesion and this effect is mediated by SNS, since bilateral functional decortication induced by cortical-spreading depression (CSD) impaired the increase of O2 consumption to the same extent as administration of propranolol. In the second experiment the role played by the cerebral cortex on thermogenesis in rats during voluntary overeating of "cafeteria" diet and in control rats was investigated. Cafeteria rats showed a significantly higher colonic temperature, brown adipose tissue temperature (Tbat), and rate of O2 consumption than control animals. CSD led to a significant decrease of Tbat and O2 consumption in cafeteria rats but not in controls. On the basis of the results obtained in the two experiments, the possibility that the cerebral cortex could be involved in the metabolic responses for reduction of body weight to the "set-point" is hypothesized.