Endothelial cells produce a variety of factors involved in the control of vascular tone, platelet activation and cell growth, the most important being nitric oxide (NO) and prostacyclin (PGI2). Although continuously produced in small amounts, synthesis and release of these autacoids are enhanced by mechanical (eg fluid shear stress) and humoral stimuli (eg acetylcholine, bradykinin, histamine). By counteracting neuro-and myogenic vasoconstriction, the continuous release of NO and PGI2 from the vascular endothelium represents a sensitive and highly effective local system for the maintenance of an adequate blood flow to the organs. This overview resumes current knowledge concerning the intracellular pathways which link endothelial cell activation by receptor-dependent and-independent stimuli to the formation of NO and PGI2.