It has been suggested that elevated plasma levels of lipoprotein(a) [Lp(a)] are associated with stenosis of aortocoronary vein grafts. To further elucidate the pathophysiology of intimal thickening or atherosclerotic plaques of the vein grafts, we investigated deposition of Lp(a) in association with cellular components of intimal lesion and with phenotypic expression of smooth muscle cells by use of immunocytochemical techniques. Seven anastomotic sites of patent grafts obtained from necropsy patients and one occluded graft from recoronary artery bypass grafting (CABG) were studied. The interval between the operation and death or re-operation in these patients varied from 9 days to 12 years. Monoclonal antibodies were used against smooth muscle cells (HHF35, CGA7), macrophages (HAM56), vimentin, T cells (UCHLl) and Lp(a) (lD1). At the anastomotic site at 9 days after CABG, no deposition of Lp(a) was found within neointimal tissue. At 1 and 9 months after grafting, anastomotic sites revealed a distinct intimal thickening showing no deposition of Lp(a). At these stages, the hyperplastic intima consisted almost entirely of smooth muscle cells of differentiated phenotype. However, in vein grafts at 11 and 12 years after CABG, marked deposition of Lp(a) was observed in intimal lesions with fibrous and atheromatous changes. At these sites, the thickened intima was composed largely of macrophages and T cells, intermixed with smooth muscle cells showing characteristic features of de-differentiated phenotype. In conclusion, these results suggest that Lp(a) deposition associated with a change of cellular composition and with phenotypic modulation of smooth muscle cells may play a key role in the development of vein graft atherosclerosis.