The method of intestinal cooling was used to analyze the effect of centrally administered ACTH in microgram quantities on hypothalamic centers regulating activity of thermoregulatory outputs (cold thermogenesis--CT, peripheral vasomotor tone--PVMT, respiratory evaporative heat loss--REHL). ACTH, when injected into the supraoptic area of the anterior hypothalamus of normal rabbits, had no significant effect on body temperature control. Intrahypothalamic administration of ACTH during the early phase of the fever, induced by intravenous injection of exogenous pyrogen, evoked dissociation of temperature thresholds for cold and warm defence, shifting the threshold for induction of cold thermogenesis to lower central temperatures. The thermosensitivity of centers controlling cold thermogenesis was lowered and the maximal values of cold thermogenesis were depressed to about 30% of those in control rabbits. Central administration of ACTH in the late phase of the fever (120 min after IV injection of endotoxin) induced a smaller effect than in the early phase of the fever--the downward shift of the temperature threshold for cold thermogenesis was less evident and the thermosensitivity of the controller remained unchanged. The changes in activity of thermoregulatory centers that occurred after ACTH in febrile rabbits correspond to those observed in the late phase of the fever in ACTH-untreated rabbits. It is suggested therefore, that the presumed increase in ACTH production during fever might represent a negative feed-back mechanism contributing to the termination of the febrile state.