The capacity of rat cerebral endothelial cells (RCEC) to form eicosanoids was determined after incubation with l4C-labelled arachidonic acid. Prostaglandin E2 (PGE2) was the main metabolite formed by RCEC and was responsible for 54% of the total amount of eicosanoids produced. In contrast, in primary cultures of rat aorta endothelial cells, 32% of the amount of prostaglandins was 6-keto-PGF1α). RCEC treated with 50 ng/ml LPS for 24 h responded with an augmented PGE2 synthesis and 6-keto-PGF1α of 3.4-fold and 2.2-fold, respectively. Cultures treated with IL-1β (50 ng/ml) for 3 h showed a stimulation of the release of PGE2 and 6-keto-PGFα of 2.5- and 4.5-fold, respectively, and 2.0-fold and 2.3-fold, respectively, after IL-6 (50 ng/ml) incubation for 3 h. PGE2 is the main eicosanoid formed by RCEC in response to inflammatory agents, suggesting an important role of the cerebral endothelial cells in the transduction of an inflammatory response in the central nervous system.