Plasma concentrations of endothelin-1 (ET-1) have been reported to be elevated in children and adults with pulmonary hypertension. We hypothesized that infants with persistent pulmonary hypertension of the newborn (PPHN) have elevated plasma concentrations of ET-1. Plasma concentrations of immunoreactive-endothelin-1 (ir-ET-1) were measured using a radioimmunoassay in 20 infants with PPHN and 20 normal term infants. Mean birthweight and gestational age of the infants were comparable in the two groups. The mean plasma ir-ET-1 concentrations were significantly elevated in neonates with PPHN compared to those of normal term infants (2.04 +/- 0.30 versus 1.04 +/- 0.29 pg/mL, p = 0.02). A linear regression analysis demonstrated a significant relationship between ir-ET-1 concentrations and alveolar-arterial oxygen gradient (r = 0.49, p = 0.02) and mean airway pressure (r = 0.49, p = 0.02). There was also a significant correlation between ir-ET-1 concentrations and duration of extracorporeal membrane oxygenation among infants with PPHN (r = 0.44, p = 0.05). We conclude that plasma ir-ET-1 concentrations are elevated in infants with PPHN. The presence of elevated ir-ET-1 concentrations and their positive correlation with disease severity suggests that ET-1 may serve as a marker of the disease severity in these infants. However, further studies are needed to elucidate the role of ET-1 in the pathophysiology of PPHN.