Experiments were designed to compare the vasodilator properties of SIN-1, the active metabolite of molsidomine, with nitric oxide (NO) and sodium nitroprusside. Rings of canine femoral arteries and veins with and without endothelium were suspended in organ chambers for the measurement of isometric force. SIN-1 and sodium nitroprusside relaxed rings of blood vessels in the presence and in the absence of the endothelium. However, these relaxations were reduced by the endothelial cells in arteries contracted with endothelin and in veins contracted with prostaglandin F2 alpha. In the arteries, SIN-1, sodium nitroprusside, and NO were equipotent in relaxing rings without endothelium contracted with either norepinephrine or prostaglandin F2 alpha; NO was less potent than the other two vasodilators when the arteries were contracted with endothelin. In the veins without endothelium, the potency of the three nitrovasodilators was comparable; the veins were more sensitive to the effects of the dilators when contracted with prostaglandin F2 alpha than with either endothelin or norepinephrine. These results indicate that SIN-1, sodium nitroprusside, and NO are potent dilators of arterial and venous smooth muscle, and that the potency of the dilators can be altered by endothelial cells and the contractile agonist differentially in arteries and veins.