The low density lipoprotein (LDL) receptor is well known for its role in mediating the removal of apolipoprotein B (apoB)-containing lipoproteins from plasma. Results from in vitro studies in primary mouse hepatocytes suggest that the LDL receptor may also have a role in the regulation of very low density lipoprotein (VLDL) production. We conducted in vivo experiments using LDLR−/−, LDLR+/−, and wild-type mice (LDLR indicates LDL receptor gene) in which the production rate of VLDL was measured after the injection of [³⁵S]methionine and the lipase inhibitor Triton WR1339. Despite the fact that LDLR−/− mice had a 3.7-fold higher total cholesterol level and a 2.1-fold higher triglyceride level than those of the wild-type mice, there was no difference in the production rate of VLDL triglyceride or VLDL apoB between these groups of animals. Experiments were also conducted in apobec1−/− mice, which make only apoB-100, the form of apoB that binds to the LDL receptor. Interestingly, the apobec1−/− mice had a significantly higher production rate of apoB than did the wild-type mice. However, despite significant differences in total cholesterol and triglyceride levels, there was no difference in the production rate of total or VLDL triglyceride or VLDL apoB between LDLR−/− and LDLR+/− mice on an apobec1−/− background. These results indicate that the LDL receptor has no effect on the production rate of VLDL triglyceride or apoB in vivo in mice.