Supernatants were obtained from human peripheral blood mononuclear cells stimulated with phytohemagglutinin or in a mixed lymphocyte reaction. The effect of mononuclear cell products on vascular prostacyclin (PGI2) production was measured using cultured rat aortic smooth muscle cells (SMC) or aortic rings. PGI2 was measured by radioimmunoassay of its metabolite, 6-keto-PGF1 alpha. Supernatants containing mononuclear cell products induced PGI2 production in vascular tissue. Supernatant-induced PGI2 production of SMC was relatively slow, requiring more than six hours of incubation with supernatants, and was completely prevented by aspirin, a cyclooxygenase inhibitor. The regulation of arachidonic acid metabolism by products of stimulated mononuclear cells, which is critical to the physiology and pathology of blood vessels, may be an important aspect of the interaction between immunocompetent cells and vascular tissue.