Two isoforms of cyclo-oxygenase (COX) have been identified; a constitutive isoform (COX-1), found in abundance in platelets and the vascular endothelium, considered important for the roles of prostanoids and a cytokine/mitogen inducible isoform (COX-2), which is thought responsible for the majority of the inflammatory prostanoid production. As a number of COX metabolites regulate vascular smooth muscle cell function and the interaction between the vessel and circulating components, we have discussed the possibility that COX-2 can be induced in, and regulate human arterial or venous smooth muscle cell function. It is now clear that COX-2 can be induced in freshly isolated vessels in culture, which can be further stimulated by addition of pro-inflammatory cytokines. Interestingly, smooth muscle cells derived from saphenous vein can release extremely high levels of prostanoids, and express greater levels of COX-2 protein than internal mammary artery cells. This difference can be accounted for by an arterial cell-specific negative feedback mechanism. In addition to inducing COX-2, certain cytokines regulate smooth muscle function, by regulating cell proliferation, adhesion, and mediator release. The effects of COX-2 activity on these smooth muscle cell responses will be further discussed.