The responses of T cells to autologous non-T mononuclear cells is called the autologous mixed lymphocyte reaction (AMLR). It seems to be an immunological response, as there is evidence of both immunologic specificity and memory. The AMLR is absent in systemic lupus erythematosis and chronic lymphocytic leukemia, and our data in normal human show that AMLR decreases with aging. Reactive T cells in the AMLR are subsequently cytotoxic to autologous B cells. We propose that the AMLR may be a protective phenomenon particularly against aberrant or neoplastic clones of B cells; and its decrease in the elderly may play an important permissive role for the development of either increased autoantibodies and/or B cell neoplasias.