The aim of the present study was to identify the site of prostaglandin E2 (PGE2) production in the brain in response to a pyrogenic dose of endotoxin. The presence of PGE2 was detected using immunocytochemistry on Bouin's fixed vibratome sections of control and endotoxin-treated rats. Peripheral administration of endotoxin caused a time-related stimulation of PGE2 immunoreactivity (irPGE2) in the choroid plexus and in the microvasculature of the brain. In addition to these sites, hypophysiotrophic neurons of the paraventricular nucleus (PVN) and supraopticus nucleus (SON) responded with induction of irPGE2 to endotoxin administration. Our data demonstrate that alterations in brain function in response to endotoxin may involve arachidonic metabolites such as PGE2 that are induced at the blood-brain barrier (microvasculature) and blood-liquor barrier (choroid plexus) and in hypophysiotrophic neurons of the rat brain.