Endothelium-dependent responses differ in arteries and veins of the dog. Experiments were performed to determine whether chronic grafting of veins into the arterial circulation would alter the endothelium-dependent responses of the veins. Segments of femoral veins were grafted to the femoral artery of the dog. 6 wk after surgery the venous grafts were removed from the dog, cut into rings, and suspended in organ chambers for isometric tension recording. In some rings the endothelial cells were removed. Acetylcholine and alpha 2-adrenergic agonists did not cause endothelium-dependent relaxations in venous grafts. The calcium ionophore (A23187) initiated such relaxations which were not mediated by prostanoids. Endothelium-dependent relaxations were also observed in venous grafts to ADP, thrombin, and arachidonic acid. In segments of graft where myo-intimal hyperplasia was prominent, relaxations to ADP, thrombin, and A23187 were blunted and in some segments contractions were observed. These results demonstrate the ability of the endothelium of venous grafts to initiate changes in tone of the smooth muscle.