Histopathological and immunohistochemical studies were carried out on five cases of canine systemic atherosclerosis. The five animals were male, and showed hypercholesterolaemia and hypertriglyceridaemia on biochemical analysis of plasma. Histopathologically, atherosclerotic lesions were seen in the aorta and muscular arteries in many organs, including the heart, spleen, kidneys, lungs, pancreas, alimentary tract, urogenital organs, eyes, prostate and urinary bladder. The lesions were characterized by the deposition of lipids and infiltration of lipid-laden foamy cells in the tunica intima and tunica media, sometimes forming fibrofatty plaques, containing abundant sudanophilic material, cholesterol clefts and mineralized material. The lesions started in the tunica intima and extended to the tunica media and tunica adventitia. Immunohistochemical examination with canine apolipoprotein B-100 (CApoB-100) antibody identified the lipids containing low density lipoprotein. Immunoreactivity to CApoB-100 antibody was recognized in the tunica intima, lipid-laden foamy cell cytoplasm and smooth muscle cells in the tunica media, and fibrofatty plaque. These histopathological and immunohistochemical features were similar to those of human atherosclerotic lesions.