The level of activity in the autologous mixed lymphocyte reaction (AMLR) was studied in populations of young and old subjects. AMLR activity was reduced in the older age group. A subpopulation of the older age group who had Alzheimer’s disease was shown to have the lowest AMLR values. Within this group, those with a history indicating a more rapid development of CNS-related disability from senescence showed the weakest AMLR responses. The AMLR values correlated neither with sex, nutritional status nor history of infections. This impairment of a central regulating immune reaction may be a significant variable in manifestations of the aging process.