High lipoprotein(a) [Lp(a)] levels form a major risk factor for the development of atherosclerosis. The risk of elevated Lp(a) concentrations is significantly increased in patients who also have high levels of LDL cholesterol. Although the relation between Lp(a) and atherosclerosis has been reported in numerous studies, little is known about whether Lp(a) would exacerbate the complicated lesion formation in vivo. To test the hypothesis that increased plasma levels of Lp(a) may enhance the development of atherosclerosis in the setting of hypercholesterolemia, we generated WHHL transgenic rabbits expressing human apolipoprotein (a) and compared the atherosclerotic lesions with those of nontransgenic WHHL rabbits.