Studies in our laboratory have shown that a fraction of apolipoprotein (apo) E internalized by hepatocytes escapes degradation and is resecreted. Although the intracellular routing is not fully understood, our studies suggest that a portion of apoE recycles through the Golgi apparatus. Given the role of the Golgi apparatus in lipoprotein secretion and the fact that apoE modulates the hepatic secretion of very low-density lipoprotein, we hypothesized that recycling apoE has an effect on hepatic very low-density lipoprotein assembly and/or secretion. To test this hypothesis, apoE-/- mice were transplanted with bone marrow from wild-type mice. In this model, extrahepatic (macrophage-derived) apoE is internalized by the hepatocytes in vivo and is resecreted when the hepatocytes are placed in culture. Unexpectedly, our studies demonstrate that recycling apoE has little effect on hepatic lipid content or hepatocyte triglyceride secretion. In addition, recycling apoE has little effect on the expression of enzymes and proteins involved in lipid synthesis as well as plasma lipoprotein apoproteins. We conclude that the physiological relevance of apoE recycling may not be related to cell-specific functions, such as lipoprotein assembly in the liver. Rather, recycling may provide a mechanism for modulating general cellular effects such as intracellular cholesterol transport or cholesterol efflux.