Since the effects of prostaglandin synthetase inhibitors on the developing human fetal pulmonary vasculature are unknown, we studied the lungs of two infants, one whose mother took salicylates and the other whose mother took indomethacin during pregnancy. Lungs were fixed by perfusion and fifth generation (resistance) vessels identified. The infant with chronic exposure to aspirin had premature constriction of the ductus arteriosus, tricuspid insufficiency, increased pulmonary arterial medial width/external diameter ratio due to increased smooth muscle, and a decreased number of pulmonary vessels/cm2 lung tissue. The infant with short-term exposure to indomethacin had hypoxemia, increased pulmonary arterial m/d ratio due to increased smooth muscle, and a normal number of pulmonary vessels/cm2 lung tissue. These abnormalities may be due to the effects of prostaglandin synthetase inhibitor drugs on the ductus arteriosus and/or the pulmonary vessels of the human fetus.