The activity of nafazatrom and molsidomine, two antithrombotic drugs claimed to increase prostacycline level, was investigated in an electrically-induced carotid thrombosis model in the conscious rat. Both nafazatrom (5 mg/kg, i.v.) and molsidomine significantly delayed thrombus formation, an activity that was shared by prostacyclin (100 ng/kg/min, i.v.). Acetylsalicylic acid, at a dosage devoided of antithrombotic activity (100 mg/kg, i.v.) abolished the effect of nafazatrom but not of molsidomine. These results indicate that a cyclooxygenase-dependent compound (prostacyclin ?) play a major role in the antithrombotic effect of nafazatrom but not of molsidomine. Moreover, since compounds inhibiting the lipoxygenase pathway, i.e., BW755c (10 and 25 mg/kg, i.v.) and nordihydroguaiaretic acid (10 and 25 mg/kg, i.v.) were unable to show any antithrombotic effect, the activity of molsidomine can unlikely be due to its lipoxygenase inhibitory property.