The discovery of the SCID mouse mutation has been an important advance for the study of human lymphopoiesis and autoimmunity. Further work in the SCID mouse models described in this review should yield important new information related to transplantation of human hematopoietic stem cells across HLA barriers, characterization of hematopoietic development in vivo, and identification of pathogenic human T cell clones in organ-specific autoimmune diseases. If pluripotent hematopoietic stem cells and pathogenic autoimmune T cells can be defined using SCID mouse recipients, this would pave the way for development of novel strategies for bone marrow transplantation and for interventional immunotherapy of autoimmune diseases targeted at the T cell receptor (99).