Fetal sheep ductus arteriosus readily synthesizes prostacyclin from exogenous prostaglandin endoperoxides, and in the presence of high oxygen tension, this synthesis is markedly suppressed. Fetal aorta and pulmonary artery also synthesize prostacyclin; however, this synthesis is much less suppressed by high oxygen tension. We propose that ductal closure may be regulated by the oxygen dependent synthesis of hydroperoxy fatty acid which would block the production of the vasodilatory prostacyclin and expose the direct contractile properties of intrinsic prostaglandin endoperoxide. This mechanism would result in ductal closure at birth.