The very low density lipoprotein (VLDL) receptor is a member of the LDL receptor family. As opposed to the LDL receptor, the VLDL receptor is expressed primarily in muscle and adipose tissue. Although the VLDL receptor is capable of binding lipoproteins, its functional role is still unclear. Previous studies found that VLDL receptor expression is unaffected by fasting in the rat. The current studies examined whether VLDL receptor expression is altered with fasting in the mouse. Balb/c mice were fasted for periods up to 48 hours, killed, hearts and epididymal fat obtained, and total membranes prepared. To detect the VLDL receptor a portion of the rat VLDL receptor was expressed as a bacterial fusion protein, purified and used to immunize rabbits. The antibodies raised specifically recognized intact VLDL receptor. When cardiac membranes were immunoblotted, VLDL receptor expression increased progressively with fasting, doubling at 36 hours. In contrast, VLDL receptor expression decreased progressively with fasting in membranes from epididymal fat, being reduced 70% by 48 hours. Thus, VLDL receptor expression appears to be regulated in mouse heart and fat by nutritional perturbation, supporting a potential role for the VLDL receptor in the delivery of triglycerides/fatty acids as fuel.