Intimal hyperplasia is a frequent cause of failure of vascular surgery and angioplasty including endarterectomy, bypass surgery, angioplasty and atherectomy. Some author reported 50% of late failure identified in 5000 arterial reconstructions, including both endarterectomy and bypass operations, were attributed to this hyperplastic intimal response. Clearly this response is a significant cause of morbidity in patients undergoing vascular procedures and investigations on methods to control this process are of great importance. The precise patholphysiologic pathways leading to the development of intimal hyperpllasia have not been characterized.The initial event is thought to be damage to the vascular endothelium. Intimal thickening is the characteristic fibromuscular cellular response of intimal injury and some author advanced the "response-to-injury" hypothesis of atherogenesis and intimal hyperplasia. The response of the medial smooth muscle cell (SMC) to vascular injury can be devided into four distinct stages: (1) an initial medial proliferative response, (2) migration from the media across the internal elastic lamina and into the intima, (3) subsequent proliferation within the neointima, and (4) synthesis and deposition of extra-cellular matrix. Ross and Gomset suggested that a high local concentration of growth factors, particularly platelet-derived growth factor (PDGF), releaed from degranulating platelets could stimulate SMC proliferation. But Clowes and Reidy concluded from their research result that platelet factors do not play a substantial role in the initial wave of proleferation after injury but do influence migration from the media to the intima. From the observation of response to the balloon injury of carotid artery, Lindner and Reidy concluded that damaged SMC might be releasing some kind of intracellular factor. A logical candidate is now basic fibroblast growth factor (bFGF) Currently the only available option for the treatment of intimal hyperplasia is mechanical intervention with revision or angioplasty of the affected vessel. The ability of several agents to suppress the development of intimal hyperplasia has been investigated and some drugs have been shown to be at least partially successful in this regard: antihypertensive drugs, antiplatelet agents, antiimflammatory agents, anticoagulants, antilipid agents, and other substances including angiopeptin, and porphyrin compounds. The variety of agents attests to the complexity of the pathways which responsible for the development of this lesion and suggests that no single agent will likely be entirely effective. Although the usefullness of pharmacologic therapy to prevent myointimal hyperplasia remains unclear, if effective pharmacologic therapy and thus prevent the assoiciated recurrent arterial stenosis, this would be major impact on the durability of vascular procedures and lower their associated morbidity, mortality and cost. Gene transfer methods are providing important information about the biology of vascular cells. The most gene transfer techniques involves the introduction of new genetic information into the genome of specific vascular cells. These genetically altered cells subsequently express individual proteins or traits for which they have been engineered. Most investigators have considered endothelial cells the ideal recipient for human gene therapy. Ths is because their location makes them easily accessible to recombinant vectors and allows for any produced products to be secreted directly into the bloodstream. In vitro experiments have already been performed that have documented the ability to transfer specific genes into cultured endothelial cells. Genes coding for neomycin resistance, b-galactosidase, growth hormone, prostacyclin, and tPA, have all been successfully transferred. More recently, expression of recombinant gene products, by transduced endothelial cells, has also been achieved in vivo. The potential of genetically engineered vascular cells to modify the vessel wall and interfere with the development of intimal hyperplasia is obvious and research into this possibility is developing rapidly. Intimal hyperplasia will continue to be a major cause of vein graft and native artery with resultant loss of life and limb. To prevent the problem successfully further understanding of the mechanism of intimal hyperplasia will be required so that treatment can be tailored to the key steps in the pathologic process. As we enter the 21st century, gene transfer, somatostatin, photodynamic theapy and brachytherapy, intravascular irradiation following angioplasty and stent insertion will be the importanat focus for research on intimal hyperplasia.