In vitro experiments on rings from coronary arteries, femoral arteries, and femoral veins of sheep were performed, and cumulative concentration-relaxation responses were established for glyceryl trinitrate (GTN) and the molsidomine metabolite SIN-1. Paired preparations of control and deendothelialized coronary artery rings were used, and the vessels were precontracted with different agonists at a concentration that elicited 30% of maximal contractions (EC-30). In coronary arteries, the responses for GTN and SIN-1 on normal and deendothelialized preparations were not significantly different. In coronary arteries preincubated with 0.44 mM GTN or SIN-1 to study tolerance development, there was a significant loss of efficacy to the relaxant effect of GTN, whereas the effect SIN-1 was essentially maintained. Femoral arteries and veins were readily relaxed with GTN. and SIN-1. In veins relaxation in relation to resting tone was much more pronounced than in coronary or femoral arteries. In conclusion, the molsidomine metabolite SIN-1 is a potent coronary and venous vasodilator that does not induce tolerance.