Platelet-derived growth factor (PDGF) may be an important regulator of vascular smooth muscle cell (SMC) replication and migration in vivo. Platelets, macrophages, endothelial cells, and SMC are all potential sources of PDGF in the vessel wall. In this study, we have examined the regulation of PDGF gene expression using human SMC cultured in vitro. These cells express transcripts encoding the PDGF A-chain, but not the B-chain. The addition of serum, phorbol ester, acidic fibroblast growth factor, transforming growth factor-β, or tumor necrosis factor-α to serum-starved SMC increased PDGF A-chain mRNA levels. The cytokines interleukin-1 and -6 had no detectable effect. These results indicate that SMC present at sites of injury or inflammation may express elevated levels of PDGF-AA, which could act locally in an autocrine or paracrine manner. © 1991 Academic Press, Inc.