Of the effects of morphine and endogenous opioid peptides on thermoregulation, the one which is most likely to be of physiologic significance is hyperthermia. This increase in body temperature is the result of coordinated changes in both physiological and behavioral thermoregulatory activities and, like fever, reflects an increase in the level about which body temperature is regulated. Morphine, endogenous opioid peptides and other opioids such as pentazocine all cause hyperthermia, but the considerable variation in the dose of naloxone required to antagonize the different agonists indicates that more than one type of opiate receptor is involved in these pharmacologic responses. The minimal effect of naloxone and naltrexone on normal body temperature and on pyrogen-induced fever indicates that endogenous opioid peptides are unlikely to act physiologically via stimulation of receptors specifically sensitive to morphine. However, methionine-enkephalin is less readily antagonized by naloxone and could have a physiologic role in thermoregulation through stimulation of another type of opiate receptor.