It is well known that cold and diet-induced thermogenesis, which is mediated in small rodents by the hypothalamic-noradrenergic fibers-brown adipose tissue axis, is impaired in genetically obese mice. To test whether these adaptive mechanisms are also impaired in obese humans, 12 young males who were otherwise healthy (6 lean and 6 obese) were examined. The obese subjects had an early-onset type of obesity with a strong family history of it as well. Deep body temperature was measured by using a deep body thermometer furnished with three thermocouples. They were respectively placed on the sternum, on the interscapular area immediately under the neck (HIS), and on the 4th intercostal space (LIS) in order to study core temperature as well as heat production where brown adipose tissue could also be present in adults. Both lean and obese subjects were kept in a thermoneutral environment (28 degrees C) until they reached a steady-state body temperature and then rapidly transferred into a cold room (6-8 degrees C) where they remained up to 60 min. Body temperature decreased in both groups, but the decrease was more marked in the obese individuals on the sternum (P less than 0.01), on HIS (P less than 0.05) and on LIS (P less than 0.05) when compared to lean individuals. In conclusion, cold-induced thermogenesis is impaired in familial early-onset human obesity and in genetically obese mice.