—In a previous work, we postulated that endothelial cells possess only the following 2 enzymes involved in prostanoid synthesis: cyclooxygenase and prostacyclin synthase. The present work focused on investigating the expression of prostaglandin (PG) E synthase (PGES) in vascular cells. After incubation of vascular smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs) with [¹⁴C]arachidonic acid, the profile of prostanoid synthesis was assessed by HPLC. Untransformed PGH₂ released by the cells was evaluated as the difference in the formation of PGF_2α in the incubations performed in the presence and in the absence of SnCl₂. Resting SMCs and SMCs stimulated with phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α formed PGE₂ and PGI₂ (evaluated as 6-oxo-PGF_1α), and in the presence of SnCl₂ only a small amount of PGE₂ was deviated toward PGF_2α. In contrast, resting and stimulated HUVECs produced PGI₂, PGE₂, PGF_2α, and PGD₂, and SnCl₂ completely diverted PGE₂ and PGD₂ toward PGF_2α. Reverse transcriptase–polymerase chain reaction analysis shows that mRNA encoding for PGES was not present in HUVECs and in endothelial cells from saphenous vein. Nevertheless, PGES was expressed in SMCs and induced by IL-1β and TNF-α, and by PMA and LPS, although to a lesser extent. Whereas SMC stimulation led to an increase in the synthesis of PGE₂ and PGI₂ but not of untransformed PGH₂, stimulation of endothelial cells resulted in an enhanced release of the vasoconstricting prostanoid PGH₂.