Under the influence of specific cytokines, endothelial cells (EC) change from a quiescent state in which cell cycling is measured in terms of years, to a rapidly replicating and highly invasive phenotype reminiscent of tumor cells. As a result, preexisting microvessels greatly increase in number (angio-genesis) and play a critical role in tissue remodeling. Angiogenesis may be physiological as in endometrial cycling or pathological as occurs in wound healing or in growing tumors. Cytokines that stimulate neovascularization repre-sent a subgroup that is collectively referred to as" angiogenic growth factors." Basic fibroblast growth factor (bFGF) was the first angiogenic cytokine to be identified (1). Although it stimulates the division of cells other than EC, bFGF established several criteria that generally characterize angiogenic growth factors. Thus, bFGF stimulates EC proliferation tn vitro, induces angiogenesis invivo, and is frequently present at sites of capillary growth (24). While proteins identified by such criteria are sufficient to induce angiogenesis (see review 4), and have been found in situ at sites of pathological angiogen-esis, it has been less clear that they afe, in fact, necessary for determining physiological angiogenesis in vivo. Vascular permeability factor (VPF), also known as vascular endothelial growth factor or VEGF (VPFA/EGF)(5), is another protein that satisfies the criteria of angiogenic stimulator. In addition to inducing angiogenesis, VPFNEGF is also implicated in the vasculogenesis of development. So-called" knock out" of VPF/VEGF by homologous