ApoE, as well as apoB100, is a major component of mammalian lipoproteins and functions in metabolism of plasma lipoproteins through its interaction with LDL receptor mainly in the liver. ApoE is also thought to be a specific ligand for putative hepatic chylomicron remnant receptor (apoE receptor). Several lines of evidence suggest that lipoproteins with several molecules of apoE have a higher affinity for LDL receptors than those without apoE, suggesting that apoE functions in determining the metabolic fate of lipoproteins containing apoB100. In transgenic mouse lines with integrated rat apoE gene under control of metallothionein promotor, the plasma level of rat apoE in homozygotes for the transgene was 17.4mg/dl after zinc induction. Overexpression of apoE enhanced the clearance of lipoproteins containing apoB100, resulting in reduced plasma triglycerides levels. To investigate the role of apoE in hepatic uptake of chylomicron remnants, kinetics of chylomicrons were studied in transgenic mouse lines. Plasma clearance of injected ¹²⁵I-labeled human chylomicrons was five-fold faster in transgenic mice than in controls. Immunohistochemistry demonstrated that apoE was specifically localized at the basolateral surface of hepatocytes of fasted transgenic mice. After injection of a large amount of chylomicrons, the density of the cell-surface apoE was markedly reduced and vesicular staining was observed in the cytoplasm, suggesting that the cell-surface apoE was used for hepatic endocytosis of chylomicron remnants.