E series prostaglandins (PGE) are known to elicit potent hyperthermia when injected into the anterior hypothalamic preoptic area (POAH) in rats, but the effector mechanisms mediating the rise in temperature are not well defined. In the present study, microinjection of PGE2 into the POAH dose-dependently increased non-shivering thermogenesis in brown adipose tissue (BAT) in urethananesthetized rats, bringing about a marked and sustained rise in interscapular BAT (IBAT) and core temperatures. The effect of intra-POAH PGE2 injection on IBAT and core temperatures could be blocked by systemic pretreatment with the sympathetic ganglionic blocker chlorisondamine chloride or the beta-adrenergic receptor blocker propranolol, thus implicating the involvement of the sympathetic system. Furthermore, the increase in IBAT and core temperatures induced by intra-POAH PGE2 could be blocked by prior injection of the local anesthetic procaine or the GABA receptor agonist muscimol into the ipsilateral ventromedial hypothalamic nucleus (VMH). Taken together, the results suggest that PGE2 increases body temperature by acting in the POAH to stimulate heat production in BAT via a sympathetic efferent mechanism located in the VMH.