We investigated whether pre-existing subendothelial smooth muscle cell (SMC) accumulations in cholesterol-fed rabbits are transformed into foam cell plaques. Twenty-four rabbits received a standard diet supplemented with 2% cholesterol for 4 or 8 weeks. Six rabbits received a supplement of 0.3% cholesterol for 35 weeks. The aorta and other systemic and pulmonary vessels were studied by immunohistochemistry for smooth muscle cells SMC (alpha-SMC actin), macrophages (RAM11), cell replication (proliferating cell nuclear antigen) and endothelial cells (von Willebrand factor; vWF). Initially the foam cell plaques were composed exclusively of foam cells of macrophage origin (MFC). In more advanced lesions SMC and collagen fibres were also present, leading to a fibrous transformation of the plaque. Cell replication was mainly located in the MFC. The endothelial cells covering the plaques showed an increased immunoreactivity for vWF which was also deposited in the interstitium between the FC. Pre-existing subendothelial SMC did not transform into FC. The newly formed FC plaques remained clearly separated from the pre-existing subendothelial SMC. The development of the plaques can be attributed not only to monocyte recruitment but also to macrophage multiplication.