Background: Persisent pulmonary hypertension of the newborn (PPHN) is often secondary to lung disease such as meconium aspiration syndrome (MAS) and is characterized by extrapulmonary right-to-left or bidirectional shunting at the foramen ovale and/or patent ductus arteriosus (PDA). Shunting at the PDA results in reduced oxygen saturation (SaO2) and PaO2 in the postductual region. However, studies have not directly evaluated simultaneous preductal and postductal blood gases and direction of ductal shunt. Objective: To evaluate the relationship between direction of ductal shunt and blood gas parameters in simultaneous preductal (right carotid artery) and postductal (umbilical artery) gases in a lamb model of MAS and PPHN. Design/Methods: Thirteen near-term gestation (139.4 ± 0.9d) lambs were partially exteriorized by C-section and ultrasonic flow probes were placed around the ductus arteriosus, left carotid and pulmonary artery. Catheters were placed in right carotid artery for preductal and umbilical artery for postductal gases. PPHN was induced by aspyhyxia via umbilical cord occlusion and meconum aspiration through the tracheal tube. Following delivery and one hour of stablization, simultaneous arterial gases were drawn from right carotid and umbilical arteries. Ductal flow (systolic max, diastolic min and mean) was recorded at the time of blood gas sampling and by convention, right-to-left was labeled negative and left-to-right was labeled positive. Left carotid and pulmonary arterial flows were also recorded. Significance was accepted as p < 0.01. Results: Blood gas samples drawn during the presence of right-to-left (or bidirectional) ductal shunt had lower postductal PaO2 and pulmonary blood flow and a significant pre- and postductal SaO2 difference (table 1). However, 58% of samples with at least a bidirectional shunt and 17% of samples with a predominantly right-to-left shunt had a pre- and postductal saturation difference of <3% (table 2). Conclusion(s): The presence of a bidirectional or a right-to-left ductal shunt is associated with hypoxemia and low pulmonary blood flow and is diagnostic of PPHN. However, nearly half of instances with bidirectional ductal shunting and a quarter of predominantly right-to-left ductal shunting were not associated with a ≥ 3% difference in pre- and postductal oxygen saturation. While presence of ≥ 3% saturation difference confirms right-to-left or bidirectional ductal shunt, absence of this difference does not rule out right-to-left ductal shunt or PPHN.