There is evidence of release of the opioid peptide beta-endorphin (beta-E) in the hypothalamus during development of fever and stress-induced hyperthermia. In the unanesthetized rabbit microinjection of beta-E in the preoptic/anterior hypothalamus (POAH) results in peripheral vasoconstriction, inhibition of evaporative heat loss, and a prolonged elevation of body temperature. These reactions are magnified with increases in ambient temperature. Injections of beta-E nearly abolish vasodilation to back heating and also postural enhancement of heat dissipation (sprawling, limb extension) in a hot environment. Beta-E has also been found to reduce the thermal sensitivity of single POAH neurons to ambient heating. However, POAH beta-E injections do not alter metabolic rate at ambient temperatures from 2 to 27 C, and to this extent beta-E-induced hyperthermia is distinct from fever. It is suggested that beta-E reduces sensitivity of POAH neurons to high ambient temperature and that this reduction leads to increased peripheral vasoconstriction, inhibition of evaporative heat loss, and modification of behavioral thermoregulation resulting in a regulated-type elevation in body temperature. A general neural model is proposed to explain the thermoregulatory effects of beta-E in the rabbit.