Spasm of the saphenous vein frequently occurs during harvesting from the leg and high-pressure distention is required to restore an adequate diameter for grafting. Forceful distention has been shown to damage the intima and media and may predispose to subsequent occlusion of the vein graft. Various pharmacologic vasodilators are capable of relaxing veins; in this study, we carried out a systematic investigation to determine the appropriate agents and concentrations for use during vein graft operations. In organ baths, human saphenous vein segments were contracted with potassium or a thromboxane mimetic, and vasodilator agents were then applied. Glyceryl trinitrate, 7.2 μg/mL, or papaverine hydrochloride, 11.9 μg/mL, caused 80% to 100% relaxation of contraction induced by potassium or thromboxane. Verapamil, 15.5 μg/mL, relaxed the potassium contraction by 100% and the thromboxane contraction by 75%. Comparison of the time course of action showed that glyceryl trinitrate had a rapid onset and a short duration of maximal action, whereas verapamil (like papaverine) had delayed onset and a long duration. A mixture of glyceryl trinitrate and verapamil combined rapid onset with long duration of action. We now use a mixture of glyceryl trinitrate and verapamil (pH 7.4) topically and intraluminally during harvesting of the saphenous vein to provide a relaxed conduit for coronary artery bypass grafting.