Abstract The response of endothelial adenylate cyclase (AC) to prostaglandins (PGE 1, PGE 2, PGF 1α, PGF 2α, PGD 2 and PGI 2) and the relationship of PGE 2 to adrenergic systems were investigated in cerebrovascular endothelial cultures. E-type prostaglandins and PGI 2 were more effective in stimulating endothelial AC (EC 50 = 3 × 10 −7M, and 3 × 10 −7M, respectively) than prostaglandins of the F-series and PGD 2 which activated AC at high doses only. A modulation of endothelial AC response to either PGE 2 or norepinephrine (NE) was observed in the presence of both agents in the system. It was manifested by a dose-dependent NE inhibition of the PGE 2-stimulated formation of cAMP, which was partially restored by phentolamine. Alpha and β-adrenergic agonists (α, clonidine and 6-fluoronorepinephrine; β, isoproterenol) also partly blocked while forskolin and PGE 2 synergistically stimulated the production of cAMP in the endothelial cultures. These findings strongly suggest that the interaction of prostaglandins and α- and β-adrenergic agonists with the AC system in cerebrovascular endothelium may play a role in the regulation of the cerebral microcirculation and/or blood pressure.