Age-related changes in the capacity of thymic grafts to promote T-cell differentiation were studied in congenic nude BALB/c mice. The results revealed that the cytolytic T-cell activity and T-cell-dependent anti-SRBC response declined exponentially with age, the former starting its decline at birth, and the latter after adulthood. In contrast, the T-cell-dependent mitogenic response to PHA and Con A stimulation and the number of Thy-1 + cells declined minimally with age of the thymic graft. These findings suggest that aging decreases the capacity of the thymus to synthesize the various factors needed for the generation of T-cell subpopulations differently with respect to the time of onset and rate of decline. In addition, results suggest that the aging thymus is also losing its ability to regulate natural killer cells.