To investigate the relationship between cytologic alterations and cellular proliferation during atherosclerotic remodeling, we examined experimental atheromatous plaques by immunohistochemistry. Plaques were formed on rabbit aortas by cholesterol-enriched diets and mechanical stimulation over a period of 2 months. Plaques were examined 1 month and 6 months after induction. We used antibodies RAM-11, HHF-35, and monoclonal anti-proliferating cell nuclear antigen (PCNA) antibody for detection of macrophages (Mphi), smooth muscle cells (SMC), and PCNA, respectively. One month after induction, the plaques revealed a thickened intima with a fibrofatty histologic pattern or accumulation of foam cells. With either histologic pattern, foam cells were found to be Mphi and proliferative activity was mainly observed in Mphi. Six months after induction, calcification and organization were seen on the induced plaques, suggesting progression of remodeling. There were fewer Mphi and more SMC compared with plaques examined 1 month after induction. Proliferative activity was observed mainly in SMC. We have demonstrated that the proliferative activity of cell types changes during remodeling of atheromatous plaques. Our results suggest an important relationship between the proliferative activity of SMC and remodeling.