Treatment of premature infants with exogenous surfactant is thought to increase the incidence of the patent ductus arteriosus (PDA) due to improved mechanics of breathing and the resultant reduced pulmonary vascular resistance. As part of a prospective, blinded, controlled study of human amniotic fluid-derived surfactant, we assessed the time of closure of the PDA, defined by Doppler echocardiographic studies, performed at 6-h intervals, and the mechanics of breathing at 6, 18, and 30 h of age in 61 infants (gestational age, 25-29 wk, and birth wt, 450-1580 g). All infants had respiratory distress syndrome as confirmed by immature surfactant phospholipid profiles determined on either amniotic fluid and/or tracheal aspirate analysis, and chest radiograph, and all had a PDA at 6 h of age. Surfactant treatment was associated with more frequent clinically determined need for treatment of the PDA, but did not prolong the patency of the ductus in infants with spontaneous closure or in those requiring treatment with indomethacin. Infants with spontaneous closure of the PDA had significantly higher dynamic lung compliances and lower oxygen requirements and were treated with lower mean airway pressures than those requiring PDA treatment, although their arterial blood gas status was the same. The dynamic lung compliance of infants with right to left ductal shunting was significantly lower than those with left to right shunting at 6 and 18 h but was not different thereafter. This study suggests that the maturity of the ductus arteriosus, reflected by its tendency to close spontaneously, parallels the maturity of the lungs, reflected by their mechanical stability, and that ductal closing is not significantly altered by surfactant therapy.