White Carneau (WC) pigeons are susceptible to both naturally occurring and cholesterol-aggravated aortic atherosclerosis whereas Show Racers (SR) are resistant. These differences are independent of total plasma cholesterol concentrations and appear to be genetically mediated as evidenced by the fact that offspring of WC and SR crosses have an intermediate level of susceptibility. Studies of the interaction of pigeon lipoproteins with pigeon peritoneal macrophages and aortic smooth muscle cells have shown that macrophages may be particularly important in the pathogenesis of cholesterol-aggravated atherosclerosis, especially when abnormal lipo-proteins such as cholesteryl ester-rich beta-very low density lipoproteins are present in the plasma. It is likely, however, that different pathogenic mechanisms are involved in naturally occurring pigeon atherosclerosis. If these mechanisms can be elucidated in the pigeon they should provide important clues into the pathological processes responsible for the individuality in atherosclerosis susceptibility in human beings.