The cytolytic ability of sensitized spleen cells to kill allogeneic target cells in vitro, a correlate of cell-mediated immune activity, was assessed in aging long-lived hybrid mice. There was about a 4-fold decline with age, of which about 2-fold could be accounted for by the decrease in relative numbers of immunocompetent precursor cell units. The terminally differentiated progeny cells of antigen-stimulated precursor cells of old mice were as efficient in killing target cells as were those of precursor cells of young mice. Thus, it would appear that a decrease in the proliferative and transforming capacities of antigen-stimulated precursor cells of old mice can account for the other 2-fold decline with age in the cytolytic activity. Cytolytic activity may not be the limiting function in resistance to tumour formation. This was indicated by the observation that resistance to allogeneic tumor cell challenge declines with age by as much as 500-fold in mice, showing only a 4-fold decline in their cytolytic activity.