The ductus arteriosus of the undisturbed fetal lamb was studied chronically by techniques that allowed direct serial measurements of the calibre of the fetal channel. When the direct actions were studied of vasoactive agents on the ductus arteriosus, prostaglandins did not dilate the vessel beyond its resting dimensions. The cyclooxygenase inhibitor, indomethacin, was a potent vasoconstrictor with a plateau of the dose-effect relationship occurring at 0.2 mg/kg. Fetuses of 95–98 days gestational age were equally sensitive to indomethacin when compared to animals near term. Although the prostaglandins, PGE1, PGE2PGF2α, PGH2, PGI2and PGG2, had no direct effect on the ductus arteriosus, PGE1, PGE2, PGH2and PGI2reversed the vasoconstrictor action of indomethacin. Autonomic nervous system mediators and blockers,i.e.,acetylcholine, atropine, norepinephrine, propranolol, phentolamine and methoxamine, had neither direct effects on the ductus arteriosus nor any influence on indomethacin-induced vasocon-striction. The same was true of angiotensin 1, angiotensin 2, blockade of conversion of angiotensin 1 to 2, serotonin, methysergide, aminophylline, adenosine, and dibutyryl cyclic AMP. Imidazole, a blocker of thromboxane synthase, had no direct effect on the ductus arteriosus, but reduced significantly the magnitude of the indomethacin constrictor action.The major finding of this investigation was the exquisite sensitivity of the ductus arteriosus to manipulations of the prostaglandin environment. The results suggest that both locally generated prostaglandins, as well as prostanoids in the circulation, may be involved in ductal patency and closure. A high degree of control is likely of the circulation of the ductus arteriosus and constriction of the fetal channel is probably the result of an active process.