High Low Density Lipoprotein (LDL) cholesterol levels are well-known to cause atherosclerotic diseases. The hepatic LDL receptor is the major determinant of plasma LDL-cholesterol levels, and as a result, a greater understanding of the regulatory mechanisms that control the expression and function of this gene is essential. Herein, we decided to examine whether the function of the LDL receptor increased in response to the cholesterol biosynthesis inhibitor, Zaragozic Acid A (ZA), which has been shown to significantly decrease serum cholesterol levels in rats.  The results demonstrated that ZA increased the binding and internalization of Very Low Density Lipoprotein (VLDL), but not of LDL. This ZA-dependent increase in the internalization rate of VLDL was unrelated to an increase in the overall expression levels of the LDL receptor at the cell surface. These results suggest that ZA could reduce plasma cholesterol levels by preventing the synthesis of LDL from VLDL.