Intimal cells from human aortic fatty streak lesions were isolated with collagenase-elastase digestion and the cellular uptake of lipoproteins fluorescently labeled with 3,3'-dioctadecylindocarbocyanine (DiI) was studied in primary culture. The majority of the cells in primary culture contained lipid droplets and the foam cells consisted of both macrophages and smooth muscle cells (SMC), identified with electron microscopy and the macrophages also using the monoclonal anti-Leu-M3 antibody. The lipid inclusions contained cholesteryl ester, as visualized with filipin staining. Arterial macrophages took up DiI-labeled acetylated low density lipoprotein (DiI-acetyl-LDL) in the same way as did monocyte-macrophages isolated from blood. DiI-labeled beta-very low density lipoprotein (DiI-beta-VLDL) isolated from cholesterol-fed rabbits, was taken up by both macrophages and SMCs. In macrophages DiI-beta-VLDL was internalized also in the presence of excess unlabeled low density lipoprotein (LDL), whereas in SMCs the uptake was partially prevented. DiI-LDL uptake was only seen in SMCs free of lipid inclusions and especially during cell growth. The present results show that, in human aortic fatty streaks, (a) both macrophages and SMCs accumulate cholesteryl ester, (b) macrophage foam cells possess active scavenger receptors capable of mediating the uptake of acetyl-LDL, and (c) macrophages are also capable of accumulating cholesteryl ester by receptor-mediated uptake of beta-VLDL.