Skin allograft rejection was studied in young (1 month) and old (8 months) female NZB/W, DBA/2, and Swiss mice. Old NZB/W mice rejected C57BL/6 skin grafts significantly more slowly than did young NZB/W mice. This disparity was not observed in DBA/2 or Swiss animals. Splenectomy did not prolong graft survival in old NZB/W mice, but did in the other groups, suggesting a deficiency in the spleen cell population of old NZB/W mice. Normal graft rejection could be restored in splenectomized old NZB/W mice by injection of large numbers of syngeneic young spleen cells (>;50 × 106). Intact old NZB/W mice were restored by as few as 5 × 106 young NZB/W spleen cells, suggesting cooperation between young and old spleen cell populations. This cooperation was demonstrated by studies in splenectomized old NZB/W mice in which the combination of 5 × 106 young and 45 × 106 old NZB/W spleen cells led to normal skin graft rejection, whereas neither young nor old alone was effective. Both young and old synergizing populations were found to require thymus derived (T) cells. One subpopulation of T cells consisting of recirculating and both antithymocyte serum- and corticosteroid-sensitive cells was deficient in old mice. This subpopulation was present in young NZB/W mice and synergized with a population of relatively steroid-resistant T spleen cells in skin graft rejection.