Morphine (M) was administered in different doses intraperitoneally (i.p.) or 50 micrograms intraventriculary (i.c.v.) to restrained and unrestrained guinea-pigs. The systemic administration of M induces a fall in body temperature which is more evident in restrained than in unrestrained guinea-pig. The intraventriculary administration of M produces a fall in body temperature in unrestrained animals, however no significant hypothermic effect was observed in restrained guinea-pig. Dexamethasone antagonized the hypothermic effect observed after the highest dose of M given i.p. The hypothermia observed after the highest dose of M was antagonized by naloxone in all conditions. These findings reemphasize the importance of restraint in determinating the action of M on body temperature and suggest that this effect probably results from stress-related hormone release from the anterior pituitary.