Elevated fibrinogen has been claimed as an independent risk factor for the development of atherosclerosis. Incorporation of fibrinogen into human atherosclerotic lesions has been demonstrated. We assessed in a rabbit model of experimental atherosclerosis, biodistribution as well as kinetics and vascular uptake of (125)I-fibrinogen. Rabbits aged 6 months were fed a 1% cholesterol supplemented diet. After experimental de-endothelialization of rabbit aorta using a Fogarthy catheter, (125)I-fibrinogen uptake was enhanced by more than one order of magnitude as compared to intact segments covered by endothelium. Six rabbits per group were examined. Even re-endothelialized segments showed a significantly higher uptake of the radiolabeled protein. Maximum arterial uptake varied between 12 (de- and re-endothelialized segments) and 24h (intact areas) after injection of (125)I-fibrinogen. In conclusion, these experiments for the first time suggest the increased uptake of radiolabeled fibrinogen in the aortic de-endothelized wall in rabbits.