The clinical prospect of radioiodinated SP-4 as an atherosclerotic plaque imaging agent was studied. The SP-4 was synthesized by a solid phase method and identified by an amino acid analysis after purification with HPLC. SP-4 was labeled with ¹³¹I and ¹²⁵I by the Chloramine-T method and purified through Sephadex G-25 column. Tewlve New Zealand rabbits were divided into an atherosclerotic group (n = 7, AR) and a control group (n = 5. NR ). All of the atherosclerotic rabbits were intravenous administrated with bovine serum albumin, then fed with high cholesterol and fat diet. ¹²⁵I-SP-4 was intravenous administrated to the rabbits of both groups. The biodistribution of ¹²⁵I-SP-4 in rabbits was investigated. The uptakes (%ID/g) in blood and thoracic aorta and abdominal aorta were calculated 4 hours postinjection. Macroautoradiography and microautoradiography were performed in 2 AR atheroscle-rotic abdominal aortas. The clearance of radioactivity from plasma was very rapid. ¹²⁵I-SP-4 was mainly excreted through kidneys. The radioactive uptakes of abdominal aorta and thoracic aorta of AR at 4hours postinjection were significantly higher than that of NR. The films of macroautoradiography showed focal accumulation of the radioactivity in the areas of a newly formed edges of atherosclerotic plaques. On the slices of microautoradiography, the obvious radioactive accumulation could be found in the atherosclerotic plaques. Thus it was seen that the SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions, it is potentially useful as an atherosclerotic plaque imaging agent.