Myocardial lesions were frequently found in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. The lesions were of two types. One consisted of a dissolution of muscle cells with inflammatory cell infiltrate. The other consisted of replacement fibrosis. The more the lumens of at least one of the three main coronary arteries were narrowed by atherosclerosis, the more the myocardial lesions occurred. The greater the number of vessels that were occluded, the more the incidence of myocardial lesions increased. From the age distribution of rabbits which died of natural causes, the average life span was estimated to be markedly shorter in homozygous WHHL rabbits than in normal rabbits. These findings suggest that WHHL rabbits suffered from ischemic heart disease, including acute myocardial infarction. Thus, this study shows that WHHL rabbits may be useful not only as a model of familial hypercholesterolemia but also for investigating the mechanisms of various clinical forms of ischemic heart disease.