Neonatal conditions associated with increased pulmonary artery pressure have an increased incidence of patent ductus arteriosus. We operated on 15 near term fetal lambs and placed mechanical occluders into or around both branch pulmonary arteries so that main pulmonary artery blood pressure could be controlled. The lambs were delivered and ventilated for 4 h. In seven lambs, the branch vessels were obstructed so that pulmonary artery pressure increased to equal aortic pressure; in eight lambs (control), the branch vessels were not obstructed. There were no significant differences between the two groups in circulating prostaglandin E2 or 6 keto F1 alpha concentrations, PaO2, pH, or PaCO2. Despite these similarities, ductus resistance in the lambs with elevated pulmonary pressure was significantly less than that in the control lambs. After the 4 h measurements, we studied the ductus in vitro. We have previously found that ductus arteriosus constriction produces ischemia of its muscle wall that limits its ability to dilate or constrict any further. Ductus from lambs with elevated pulmonary pressure had a significantly increased ability to respond to oxygen, prostaglandin E2, and indomethacin compared with ductus from control lambs; these findings are consistent with less ductus constriction in vivo. Thus, the high incidence of patent ductus arteriosus in neonates with elevated pulmonary vascular resistance may be due in part to the increased pulmonary vascular pressure, which opposes ductus constriction and preserves ductus responsiveness. Conversely, the normal drop in pulmonary pressure that occurs in full term infants may facilitate the closure of the ductus after delivery.