Intimal proliferation is a characteristic feature of arteriosclerosis. Whole vessel wall organ culture systems have been developed to study the early stages of neointima formation. We have cultured a large number of explants of human saphenous vein specimens for several weeks, and have identified the nature of the cells in the newly formed intima by a panel of monoclonal antibodies recognizing endothelial cells (von Willebrand factor, platelet endothelial cell adhesion molecule-1 and EN-4 antigen), smooth muscle cells (monoclonal antibodies HHF35 and CGA-7) and fibroblasts (5B5 antibody). In addition we determined the uptake of fluorescently labelled acetylated low density lipoprotein by the surface cells of the explants. We found that an apparent neointima was formed in the vein organ system, the cells of which were predominantly smooth muscle cells and originated from the cut edges and from the adventitia of the vein segment. The endothelial cells originally lining the luminal surface of the vessel segments became overgrown by these cells. They remained at the base of the newly formed neointima and a number of them reorganized into capillary-like structures. Our data suggest that explant culture of saphenous vein does not reflect the classical concept of neointima formation, in which intimal smooth muscle cells migrate through the internal elastic lamina and accumulate in the intima. Although it has this limitation, the model may serve well to study specific aspects of cell migration, smooth muscle cell differentiation and angiogenesis, and may reflect aspects of intimal thickening at surgical suture sites.