We experienced a patient who suffered from severe hypothermia. The etiology and mechanism of hypothermia were not known. Intraperitoneal (i.p.) injections of the patient's serum into restrained rats produced a significant hypothermia without associated changes in tail skin temperature. Heat balance of rats was then measured with direct and indirect calorimetry before and during the i.p. injection of the patient serum. The hypothermia induced by the patient's serum was associated with a reduction of oxygen consumption, but was not accompanied by changes in evaporative and nonevaporative heat loss. The results suggest that cryogenic substance(s), which was excessively produced in patient's blood, may affect thermogenic function and then produce hypothermia in rats.