Endothelial cells derived from human brain capillaries (HBCEC) synthesize prostaglandin D2 (PGD2) which can be stimulated, among other prostanoids, by endothelin 1 (ET-1). Both the PGD2 induced by ET-1 and the exogenously added PGD2 to HBCEC are converted to 9 alpha, 11 beta-prostaglandin F2 (9 alpha, 11 beta-PGF2), a known potent vasoconstrictor. Exogenous PGD2 also dose-dependently enhanced the production of vasoconstrictive PGF2 alpha, thromboxane B2 (TXB2), and the vasodilatory PGE2 as well as cAMP by HBCEC. The PGD2-induced formation of PGF2 alpha, PGE2, and TXB2 was reduced by the cyclooxygenase inhibitors acetylsalicylic acid (ASA) or indomethacin (Indo), indicating for the first time that PGD2 may contribute to the formation of prostanoids in HBCEC. These results strongly suggest that PGD2 may play an important role in the regulation of cerebral capillary function under physiologic and pathologic conditions.