Arterial intimal proliferation occurs in response to acute and chronic injuries such as angioplasty, surgical trauma, immune injury, and hyperlipidemia. Although there are subtle differences, all lesions contain smooth muscle cells, macrophages, and occasional lymphocytes imbedded in an extracellular matrix. The vascular injury elicits a cascade of chemotactic and mitogenic substances that augment and induce gene expression of growth factors such as platelet-derived growth factor, insulin-like growth factor, basic fibroblast growth factor, epidermal growth factor, and their receptors. Binding of the mitogenic polypeptide growth factors to their specific cell surface receptor stimulates intracellular messengers such as tyrosine kinases, cyclic AMP, protein kinase C, phosphoinositol, and calcium, resulting in expression of oncogenes like c-fos, c-jun, c-myc and c-myb. Although the molecular mechanisms for intimal smooth muscle cell proliferation are far from elucidated, the increasing understanding of the molecular mechanisms involved has enabled the demonstration of inhibition of myointimal hyperplasia in animal models by antisense oligonucleotides and experimental gene transfer.