Exposure to moderate cold for a few weeks causes adaptation through the development of nonshivering thermogenesis primarily in the brown adipose tissue. Exposure to severe cold by repeated short exposures also causes adaptation but by mechanisms that seem to be different. These latter results were confirmed in mice. It was also found that this type of adaptation is nonspecific because it can be produced by other stresses such as swimming or fasting. Simultaneous determinations of glycogen in the liver and soleus and tibialis muscles indicated a possible role for this substrate in cold resistance. Repeated cold exposure (8 times at -15 degrees C for 10 min), swimming for 3 h, or fasting for 48 h--all reduced the glycogen stores when measured immediately after the stress. However, the levels of glycogen were significantly increased above the initial values (P less than 0.01) when the determinations were made 24 h later. Cold tolerance measured by resistance to hypothermia at -5 degrees C was improved only when the test was done 24 h after the stress had taken place. Thus, cold resistance, as described in this study, is nonspecific and our results suggest that glycogen stores could serve as a rate-limiting substrate.