Regulatoy effect of heparin on the growth of porcine aortic endothelial cells was examined. Heparin did not stimulate the growth of endothelial cells by itself, while it potentiated the effect of endothelial cell growth factor (ECGF) from bovine brain. In the presence of ECGF, heparin stimulated the growth of endothelial cells in a dose-dependent manner, and protamine neutralized the effect of heparin. Other glycosaminoglycans such as heparan sulfate and dermatan sulfate had no effect on endothelial cell growth. Affinity chromatography on a heparin-Sepharose column has shown that ECGF has a strong affinity for heparin. These observations suggest that heparin binds specifically to ECGF and thus influences the growth of endothelial cells.