Myointimal hyperplasia (MIH) is an arterial wall smooth muscle cell (SMC) proliferative disorder. This process is responsible for a significant number of early and long-term arterial reconstructive and graft failures. Histopathologically, this process is characterized by a proliferation of SMC in the intima of traumatized arteries resulting in arterial and/or anastomatic stenosis with secondary thrombosis. In vitro studies of cultured SMC have allowed the evaluation of SMC response to factors suspected of being clinically associated with MIH. Principal among these is platelet derived growth factor (PDGF), which is known to be secreted by several cell types including endothelial cells (ECs) and monocytes as well as being stored and secreted by platelets. PDGF, somatomedin-C, epithelial growth factor, insulin, and other factors have been found to significantly increase SMC replication in vitro. Lipoproteins may be important substrates for SMC proliferation in contrast to heparin, which may directly inhibit SMC protein synthesis. Unlike SMCs, whose continued growth in culture is dependent on various growth factors and nutrients, ECs essentially cease to proliferate after the cells have formed a monolayer over the available surface. Extracellular matrix proteins, polypeptide mitogens, and heparin have been shown to modify EC migration and proliferation in vitro. Wounding of EC monolayers by scratching results in increased replication and migration, processes which require plasma factors that remain poorly defined. However, two general forms of EC growth factor have been isolated from many body tissues, are potent stimulators of capillary endothelial growth, and appear important both for normal EC monolayer homeostasis and for the response to injury. Cultured ECs produce mitogens for SMC. Production of the principal mitogen, PDGF, is significantly increased in sparse versus confluent cell cultures as well as by toxic agents such as endotoxin and phorbol esters. Acetyl low density lipoprotein as well as omega-3 fatty acids may significantly and selectively inhibit EC PDGF production, a finding with potentially profound implications for the clinical control of MIH in vivo.