The mechanism underlying the hyperthermic response to low doses of morphine has been investigated in rats. Doses of morphine sulfate less than 10 mg/kg i.p. caused a rise in body temperature accompanied by vasoconstriction of the cutaneous blood vessels of the tail. This hyperthermia, unlike the hypothermia following higher doses of morphine was not blocked by naloxone nor did tolerance develop to the response. Injections directly into the hypothalamus suggested that, as with the fall in temperature after high doses of morphine, the hyperthermic effect is also due to an action on the preoptic/anterior hypothalamic thermoregulatory centers. Experiments measuring thermoregulatory behavior showed that rats delayed escaping from a heat load after low doses of morphine even though their core temperature was rising. These results suggest that low doses of morphine raise the set point of the central thermostats in rats resulting in a hyperthermia mediated, at least in part, by decreased cutaneous heat loss.