The enzyme 3-Hydroxy-3- Methylglutaryl Coenzyme A Reductase catalyzes the rate limiting step of hepatic cholesterol biosynthesis and is unique among the enzymes in the early part of the pathway in that it is membrane bound. This gives rise to potential regulation of the enzyme through interactions with the endoplasmic reticulum membrane. A purification procedure has been developed which consistently produces enzyme of high specific activity. In order to fully characterize the interactions between HMG-CoA reductase and the lipids in its immediate environment, HMG-CoA reductase was purified to homogeneity and shown to be a protein-lipid complex.