Neovascularization of developing, repairing or neoplastic tissues is regulated, at least partially, by a family of proteins of low molecular mass (1000 less than mol mass less than 50 000 Da) which can be extracted from avascular tissues, such as hyaline cartilage, aorta or bladder epithelium, by mild salt solutions. These extractable proteins, functionally defined as anti-invasion factor (AIF), act as local regulators for some of the major mechanistic pathways by which endothelial cells are thought to invade tissues during neovascularization, mainly by matrix-degrading enzymes and by increased rates of migration and proliferation. AIF contains a spectrum of proteinase (collagenase) inhibitory activities, as well as an endothelial cell growth inhibitor. The endothelial cell growth inhibitor is directed against actively dividing endothelial cells in culture but has no effect on endothelial cell monolayers or any other cell lines tested. In tumours, the AIF-derived endothelial cell growth inhibitor may limit tumour growth to less than 2 mm in diameter by inhibiting tumour neovascularization.