We treated a young female patient who suffered from severe hypothermia. The etiology of the hypothermia was not identified, though various medical examinations were performed. Intraperitoneal (i.p.) injections of the patient's serum produced a significant and profound hypothermia in rats that was not associated with circulatory shock. The patient's serum was separated into 4 fractions by the use of various types of centrifugal filtration units according to molecular weights (MW), i.e., below 10 kDa, 10-30 kDa, 30-100 kDa, and beyond 100 kDa. The first two fractions never induced hypothermia in rats, but the i.p. injections of the fraction with MW from 30 to 100 kDa consistently produced hypothermia. The fraction with MW beyond 100 kDa caused marked hypothermia in one out of 3 rats tested. The results suggest that the patient was excessively producing endogenous cryogenic substances of which MW may be greater than 30 kDa.