Morphological and immunohistochemical studies using the anti-macrophage monoclonal antibody RbM2 were performed in cholesterol-fed rabbits. From the beginning of the experiment, the levels of lipoproteins showed the pattern of familial type III hyperlipoproteinemia patients, and glomerular endothelial and mesangial cells had lipid deposits. By the 3rd week, RbM2-positive cells appeared in the capillary lumina. These cells became larger and increased in number after the 8th week. Although they had become very large and had increased noticeably by the 20th week, few sclerotic glomeruli were observed. We could hardly detect any proliferation of or foamy changes in the mesangial cells, and monocyte/macrophages showed no proliferative capacity within the glomeruli. These findings suggest that hyperlipidemia alone did not cause proliferation or foam transformation of the mesangial cells. The glomerular macrophages, probably derived from circulating monocytes, did not induce a glomerular injury under the short-term hyperlipidemic conditions of these experiments.