Prostaglandin E2 (PGE2) acts in the preoptic area (POA) of the mammalian hypothalamus to increase body temperature and heart rate. Chemical stimulation of the dorsomedial hypothalamus (DMH), a region richly innervated by neurons in the POA, evokes sympathetically-mediated increases in heart rate and body temperature. We tested the hypothesis that neurons in the DMH mediate hyperthermia and tachycardia resulting from the action of PGE2 in the POA. Microinjection of PGE2 150 pmol/15 nl into the POA in urethane-anesthetized rats caused increases in body temperature and heart rate that were sharply reversed after injection of muscimol 80 pmol/100 nl into the DMH but not after similar injection of saline vehicle. Therefore, thermogenic and tachycardic actions of PGE2 in the POA are at least in part a consequence of neuronal activity in the region of the DMH.