Acid secretory and mucosal ulcerogenic responses to hypothermia (36-24 degrees C) were examined in anesthetized rats, and the role of thyrotropin-releasing hormone (TRH) in these responses was investigated. Lowering of body temperature (less than 32 degrees C) induced acid hypersecretion and damage in the gastric mucosa. These responses reached a maximum at a body temperature of 28 degrees C and were completely abolished by bilateral cervical vagotomy and significantly inhibited by intracerebroventricular (i.c.v.) administration of TRH antiserum (10 microliters/rat). TRH (10 micrograms/rat) given i.c.v. to the normothermia rat, caused an increase of acid secretion with a pattern similar to those observed during hypothermia. The blood levels of thyroid-stimulating hormone rose significantly during exposure of cold, and this response preceded the onset of acid hypersecretion and lesion formation. Thus, lowering of body temperature induces vagal-dependent gastric acid secretion, probably mediated by TRH released in response to cold exposure, and may be an important element in the etiology of stress ulceration.