To define the local effects of prostacyclin (PGI₂) on the growth of vascular smooth muscle cells (VSMC), we transfected VSMC with an expression vector harboring the cDNA for PGI₂ synthase (PGIS), which catalyzes the rearrangement of prostaglandin H₂ to PGI₂. Transfection of the human PGIS cDNA into rat VSMC did not affect DNA synthesis under serum free basal conditions, but it increased PGI₂ synthesis and decreased DNA synthesis under serum-stimulated conditions (in the presence of 1 or 5% fetal calf serum). These results demonstrated that locally synthesized PGI₂ can exert autocrine and/or paracrine inhibitory effects on VSMC growth. It was also suggested that in vivo transfer of PGIS gene may be useful for the gene therapy for vascular disease such as neointimal hyperplasia.