We examined the behavior of rabbit factor XI (rabbit F. XI) in Watanabe-hereditable hyperlipidemic rabbit (WHHL rabbit), to study the participation of F. XI in atherosclerosis. Rabbit F. XI was isolated with use of anti-human F. XI monoclonal antibody-Sepharose. Purified rabbit F. XI was single band in sodium dodecylsulfate polyacrylamide gel electrophoresis (M. W.: 80, 000), and the specific coagulant activity was 75unit/mg protein. 125I-rabbit F. XI, iodinated with Bolton-Hunter reagent, was administered intravenously to WHHL rabbit and Japanese white rabbit (normal). Then blood was taken from ear vein and the trichloroacetic acid precipitate of plasma was counted. Turnover of 125I-rabbit F. XI was significantly faster in WHHL rabbit (T1/2=2.84±0.44 days) than in normal (T1/2=4.44±0.42 days). By en-face autoradiography, specific accumulation of 125I-rabbit F. XI was observed in thoracic aorta of WHHL rabbit. In contrast, no radioactivity was observed in normal. These results suggest that activation of F. XI proceeds on the atherosclerotic lesion of WHHL rabbit.