In certain forms of congenital heart disease, patency of the ductus arteriosus is critical for survival. Since the administration of prostaglandin is associated with adverse side effects, this study was undertaken to evaluate the effects of nitroglycerin and nitroprusside on ductal blood flow during oxygen-induced ductal closure. Fifteen near-term fetal lambs were instrumented acutely. Ductal blood flow and pre- and post-ductal pressures were monitored continuously. After obtaining control data, intravenous bolus injections of nitroglycerin (250 micrograms), nitroprusside (250 micrograms), or prostaglandin E1 (5 micrograms) were administered during ventilation with either 100% nitrogen or 100% oxygen. All three agents significantly increased ductal blood flow during nitrogen ventilation (PO2 = 15 +/- 1 mm Hg). When the lambs were ventilated with 100% oxygen, the arterial PO2 increased to 107 +/- 14 mm Hg, and this was associated with a marked decrease in ductal blood flow from 275 +/- 44 to 83 +/- 11 ml/min (P less than 0.05). When nitroglycerin was administered during oxygen-stimulated ductal closure, ductal blood flow increased 184%, from 79 +/- 18 to 225 +/- 18 ml/min (P less than 0.05); nitroprusside increased ductal blood flow 126%, from 86 +/- 20 to 195 +/- 25 ml/min (P less than 0.05); prostaglandin E1 increased ductal blood flow 110%, from 84 +/- 18 to 178 +/- 17 ml/min (P less than 0.05). These data demonstrate that both nitroglycerin and nitroprusside are potent vasodilators of the ductus arteriosus and, like prostaglandin E1, can markedly attenuate the oxygen-induced ductal vasoconstriction. These results imply that nitroglycerin and nitroprusside may be useful clinically in maintaining ductal patency.