To evaluate the acute effects of surfactant replacement therapy on pulmonary circulation in neonatal respiratory distress syndrome, we studied 25 infants before and for 1 hour after either synthetic surfactant administration (n = 15) or endotracheal suctioning (n = 10). The noninvasive Doppler method was used to estimate systolic pulmonary artery pressure from tricuspid regurgitant flow velocity and to measure blood flow velocity of the left-to-right shunt through the ductus arteriosus. Pulmonary artery pressure decreased significantly within 15 minutes after surfactant administration and remained low throughout the study period, whereas suctioning did not change pulmonary artery pressure levels. No changes in systemic pressure were found in either group. Velocity of the ductal left-to-right shunting increased and remained elevated for 1 hour only in surfactant-treated infants. In addition, right-to-left ductal shunting disappeared in four infants after surfactant administration. Our data thus indicate that administration of synthetic surfactant to infants with respiratory distress syndrome reduces pulmonary vascular resistance, resulting in a decrease in pulmonary artery pressure and an increase in ductal flow velocity.