A fundamental property of vascular endothelial cells is the ability to proliferate and form a network of capillaries. 12 This process is known as" angiogenesis" and requires at least three steps: i) degradation of the extracellular matrix of a local venule, ii) chemotaxis of endothelial cells toward an angiogenic stimulus, and iii) proliferation of endothelial cells. 1, 2 Angiogenesis is prominent during embryonic development and somatic growth but in a normal adult it only takes place following injury or, in a cyclical fashion, in the endometrium and in the ovary. 1, 2 Angiogenesis plays a significant role in the pathogenesis of a variety of disorders including cancer, proliferative retinopathies, rheumatoid arthritis or psoriasis. Therefore, inhibition of angiogenesis may constitute an attractive strategy for the treatment of such disorders. Conversely, disorders characterized by inadequate tissue perfusion such as obstructive atherosclerosis and diabetes are expected to benefit from agents able to promote endothelial cell growth and angiogenesis. A variety of factors have been identified as potential positive regulators of angiogenesis: aFGF, bFGF, EGF, TGF-a, TGF-/3, PGE2, monobutyrin, TNF-a, PD-ECGF, angiogenin and interleukin-8. 1, 2 This article will review a recently identified family of directly-acting endothelial cell mitogens and angiogenic factors known as vascular endothelial growth factor (VEGF) or vascular permeability factor (VPF). 3, 4 These factors are products of the same gene and, by alternative exon splicing, may exist in four different isoforms. 5-8 Recent studies point to VEGF as a major regulator of physiological and pathological angiogenesis. Furthermore, the angiogenic activity of VEGF appears to be sufficient to achieve therapeutic benefit in animal models of coronary or limb ischemia.