In this study, we use Brij 98 to determine the lipid domain distribution of the ER proteome in rat liver microsomes with emphasis on that of the P450 enzyme system. Because of the profound effects of phenobarbital treatment on protein expression and lipid biosynthesis, we will examine the liver ER proteomes from both uninduced and phenobarbital-treated rats in order to determine if protein and lipid variability influence the domain localization of proteins. To ascertain possible functional roles associated with membrane domain localization, we will apply G.O. analysis and Ingenuity Pathway Analysis (IPA) to the proteins from the identified membrane domains. The biological processes, molecular functions, and cellular pathways associated with the membrane lipid domains will be described, and the potential biological implications of these associations will be discussed.