SIN-1, the metabolite of molsidomine, caused a dose-dependent inhibition of the aggregation of rabbit platelets induced by adenosine diphosphate (ADP) and the stable thromboxane mimetic U-46619. Molsidomine was inactive in this respect. In the presence of a threshold concentration of prostacyclin, the antiaggregating activity of SIN-1 became more pronounced. As a result, the dose-response curve of SIN-1 was shifted to the left. These findings suggest that SIN-1 could be of therapeutic value to suppress platelet aggregation during atherosclerotic disease when the endogenous supply of endothelium-derived relaxing factor is compromised.