In humans chronically infected with Schistosoma mansoni, total hepatic blood flow and normal hepatic function appear to be maintained by neovascularization of the periportal fibrotic tissue. To identify possible stimuli for this neovascularization, we evaluated parasite- derived products for their ability to activate endothelial cells in vitro. Soluble egg antigen (SEA) of S. mansoni at concentrations as low as 30 ng/mL induced a marked proliferation of human umbilical vein endothelial cells (HU VE) that increased in a dose-dependent fashion; equivalent effects were seen with bovine adrenal and murine lung endothelial cells. Live, intact S. mansoni eggs secreted a soluble factor that stimulated HUVE in a manner similar to crude SEA. In contrast, adult worm extracts of S. mansoni had no significant effect on endothelial cell proliferation in any of the three cell lines tested. Preliminary biochemical characterization showed the activity to be protease sensitive and heat stable. S. mansoni SEA, in the absence of inflammatory cells, can stimulate endothelial cell proliferation in vitro. © 1988 by the University of Chicago.