The lpr gene has been identified as a defect in the Fas gene, which encodes a lymphocyte surface protein associated with apoptosis and shares homology with the tumor necrosis factor-alpha receptor. This finding is important as it may quickly lead to identification of the gld gene product, which is thought to be a ligand for Fas. Also, it clearly identifies autoimmune disease as originating from a defect in the ability to induce cell death in lymphocytes. The major challenge in the future will be to directly demonstrate the relationship of abnormal apoptosis pathways to the development of autoimmunity and, in the case of lpr and gld mice, to lymphadenopathy, and to eventually determine if this is a fundamental defect at the root of all autoimmune diseases in both mice and humans.