Administration of prostaglandin synthetase inhibitors directly to the fetal sheep has been shown to cause constriction of the ductus arteriosus and pulmonary hypertension. Since these drugs are given to pregnant women we sought to determine if the same effect occurred in the fetus with administration of such an agent to the pregnant ewe. Pregnant ewes were operated upon at 123, 124 and 135 days gestation. Catheters were placed into the fetal pulmonary (PA) and carotid arteries (CA), the superior vena cava and amniotic cavity and the maternal inferior vena cava and aorta. Starting the first postoperative day one ewe was given indomethacin 0.5 mg/kg I.V., another 1.0 mg/kg I.V., and the other 1 mg/kg PO TID for 3 to 4 days. Initially PA and CA pressures were equal however PA pressures rose to 8, 6, and 9 mmHg greater than CA pressures by 1, 2, and 4 days respectively. Fetal blood was analyzed by spectrophotofluorometry for indomethacin and was positive for indomethacin although at very low levels. Administration of indomethacin to the pregnant ewe by either intravenous or oral routes probably crosses the placenta and causes constriction of the fetal ductus arteriosus. Direct vaso-constriction of the pulmonary vascular bed may also occur. This may have profound effects on the fetal systemic and pulmonary circulations which may be detrimental to the fetus and newborn. Supported by AHA Grant-In-Aid 76-878.