The creation of bone marrow and fetal liver chimeric mice has proven to be a valuable tool in the field of immunology. Chimeric mice are used to study the contribution of various cell types of hematopoietic versus non-hematopoietic origin in the course of an immune response. In this chapter, we describe a detailed method to obtain bone marrow or fetal liver chimeric mice and assess the efficiency of donor cells to repopulate the hematopoietic compartment of recipient mice.