Experiments were designed to determine the role of the endothelium in the responsiveness of the arterial wall to anoxia. Paired rings of canine femoral arteries were mounted for isometric tension recording in organ chambers filled with aerated Krebs-Ringer bicarbonate solution (37 degrees C). One ring served as control; in the other the intimal layer was removed mechanically. Anoxia was induced by gassing the organ chamber with 95% N2/5% CO2. In control rings anoxia augmented contractile responses to noradrenaline, KCl and BaCl2. On return to O2 the contractile responses were transiently depressed. Removal of the endothelium reduced the anoxic augmentation, but did not affect the post-anoxic inhibition. Indomethacin did not affect the response to anoxia. Anoxia abolished the endothelium-dependent inhibitory effect of acetylcholine and thrombin, reduced that of adenosine triphosphate, but augmented that of arachidonic acid. These experiments indicate that endothelial cells may contribute to anoxic facilitation of the responsiveness of the canine arterial wall.