Mice exposed to 5° C show a drop in body temperature at a time when they are more sensitive than normal mice to bacterial lipopolysaccharide (LPS). Injection of 5 mg cortisone acetate protects against the lethal effects while 8 units but not 2 units of ACTH enhance lethality. These data suggest that adrenocortical exhaustion due to cold is in part responsible for the altered sensitivity to LPS. In support of this interpretation is the increase in urine volume and urinary nitrogen excreted by mice at 5° C compared with those at 25° C. Endotoxin decreases both. The decrease is counteracted by cortisone administration but not by ACTH.