The clinical significance of lipoprotein-X (Lp-X) induced by intravenous infusion of 10% fat emulsion was assessed, with special reference to atherogenesis, by in vitro experiment using purified Lp-X from the sera of patients receiving Intralipid 10%. Lp-X appeared after long-term intravenous infusion of 10% fat emulsion in the patients with intestinal fistula due to the anastomotic leakage. To clarify the role of Lp-X in terms of atherogenicity, the cholesterol metabolism of Lp-X in macrophages as scavenger cells and in hepatocytes as parenchymal cells was studied. When [3H]cholesterol-labeled Lp-X or oxidized low-density lipoprotein (o-LDL) was incubated with J-774 macrophages, the incorporation of Lp-X into macrophages was negligible compared with o-LDL. When Lp-X or high-density lipoprotein (HDL) was incubated with J-774 macrophages laden with [3H]cholesterol, the release of cholesterol from macrophages was enhanced by Lp-X as well as HDL. When [3H]cholesterol-labeled Lp-X LDL or HDL was incubated with the human hepatoma cell line of Hep G2 cells, the incorporation of Lp-X into Hep G2 cells was less than that of LDL, but similar to that of HDL. From these findings, it is suggested that the catabolism of Lp-X cholesterol generated with intravenous 10% fat emulsion was mediated by hepatocytes rather than by macrophages, indicating that the hyperlipidemia due to increased Lp-X may not be atherogenic.