Significance Two distinct and interconvertible types of endothelial cells are present during blood vessel growth: tip cells at the growing front of the vascular network and stalk cells behind the front. In the present study, overexpression of Endothelin-2, a peptide previously implicated in the control of blood pressure, is shown to promote the tip cell fate and arrest vascular growth within the mouse retina. Genetic experiments show that this effect requires Endothelin receptor A expression in the neural retina, implying the existence of a retina-derived regulator of vascular growth and development that is under Endothelin control.