Injection of adult CBA mice with lymphocytes from C3H × CBA donors leads to a specific reduction of the MLC reactivity of the recipients’ lymphocytes. This effect is mediated by a population of Fl-lymphocytes which do not seem to possess the relevant MLC-stimulatory Mls-antigen. In this investigation we have shown that injection of C3H × CBA mice with CBA, but not C3H spleen cells enhances the ‘tolerogenic’ capacity of their thymocytes and lymph node cells. A similar enhancing effect was achieved by ‘educating’ C3H × CBA lymphocytes in irradiated CBA, but not C3H hosts. The results indicate that C3H × CBA lymphocytes reduce the MLC-reactivity by reacting immunologically against CBA T-cells which possess recognition structures for the relevant Mis antigen. Lymphocytes of C3H × CBA mice can be sensitized against such recognition structures which thus renders them more ‘tolerogenic’.