We have previously reported that intracerebroventricular injection of prostaglandin E2 (PGE2) induces hyperthermia possibly through EP1 receptors in the rat. In the present study, to determine the sites in the brain where PGE2 induces hyperthermia through EP1 receptors, we microinjected an EP1 receptor agonist, 17-phenyl-omega-trinor PGE2 (17-Ph-PGE2, 100 ng) into different sites in the rat brain and observed the colonic temperature (Tco) for 2 h in a 23 +/- 1 degrees C environment. Responsive sites where 17-Ph-PGE2 (100 ng) produced a rise in the Tco of more than 1.1 degrees C within 60 min after injection were found in the medial preoptic area, the subchiasmatic portion of the median preoptic nucleus, the anterior wall of the third ventricle (A3V) and the ventral portion of the diagonal band of Broca. Among these sites, the A3V was the most responsive. In contrast, microinjection of neither butaprost (an EP2 agonist, 100 ng) nor M&B28767 (an EP3 agonist, 100 ng) into these four sites had any effect on the Tco. Intracerebroventricular pretreatment with SC-19220 (an EP1 antagonist, 100 microg) inhibited the rise in the Tco which was induced by microinjection of PGE2 (50 ng) into the A3V. These results thus suggest that PGE2 induces hyperthermia by stimulating EP1 receptors in the A3V and the neighboring preoptic region.