Endothelin-1 is a mediator of hypoxia-induced pulmonary hypertension and pulmonary arterial remodeling, and may be involved in the pathogenesis of persistent pulmonary hypertension of the newborn and bronchopulmonary dysplasia, causes of mortality and morbidity in newborn infants. Blockade of the endothelin-A receptor was earlier shown to attenuate hypoxia-induced pulmonary hypertension and in this study, was also shown to prevent and partially reverse hypoxia-induced pulmonary vascular remodeling induced by chronic hypoxia in a newborn mouse model. These results indicate that endothelin-A receptor blockade is of potential therapeutic significance in neonates with pulmonary hypertension and abnormal pulmonary arterial remodeling.