Human retinal pigment epithelial (RPE) cells in culture were found to release a substance (or substances) that causes the regression of new blood vessels on the chick embryonic yolk sac and inhibits proliferation of fetal bovine aortic endothelial cells and human retinal microvessel endothelial cells in vitro. Neither astrocytes nor fibroblasts under identical test conditions released detectable inhibitors of neovascularization or endothelial cell growth. Subconfluent and superconfluent cultures of human RPE cells released higher levels of inhibitor than confluent cultures.