Formation of new blood vessels is vital during embryogenesis, essential for reproduction and wound healing during adulthood and required to rescue tissue during ischemia. Neovascularization may, however; also contribute to the pathogenesis of several disorders, including tumorigenesis, diabetic vasculopathy, and chronic inflammation. initially, blood vessels form as endothelium-lined channels by in situ differentiation of endothelial cells. Subsequently, they sprout and remodel into a highly organized and interconnected vascular network. During further maturation of the blood vessels, a sheet of primitive vascular smooth muscle cells surrounds the endothelium-lined channels, which controls endothelial cell function and provides structural support. Recent molecular analyses have identified candidate molecules that affect these processes. Their in vivo role has been further established by targeted gene manipulation in transgenic mice. This review highlights recent developments in the genetic analysis of blood vessel formation, as deduced from analysis of gene-inactivated mice. (C) 1997, Elsevier Science Inc.