There is a long-held belief that preterm newborns lack sufficient arteriolar musculature to maintain a prolonged elevated pulmonary vascular resistance (PVR) after birth. Net ductal flow is thought to be minimal, with the developing pulmonary circulation incapable of significant vasoconstriction. We identified retrospectively 15 premature newborns over a 10-year period weighing < or = 1500 g and with a gestational age of < or = 30 weeks with documented persistent pulmonary hypertension of the newborn (PPHN) in the first 24 hours after birth. We matched 36 newborns of similar weight and gestation with no clinical evidence of shunting. The control group weaned to an FiO2 < or = 0.50 by 12 hours after birth. Despite similar gestational ages, the PPHN group (n = 15) had significantly higher birth weights than the control group (n = 36). The duration of ruptured membranes, maternal tobacco use, and use of antenatal steroids were significantly higher in the PPHN group. We speculate that these three factors might act in a synergistic relationship with which to accelerate pulmonary vascular smooth muscle development in premature newborns.