SUMMARYFurther experiments to determine the potentialities and fate of small blood lymphocytes causing acute transplantation disease are described. Sensitive transplantation tests for chimerism were made by C57BL ± A/J skin homografts to adult recipients that had previously received an i.p. injection of most of the lymphoid tissue from individual, potential A/J runts. Accelerated graft rejection indicated that as few as 100,000 C57BL nucleated cells or their descendants had persisted in A/J young until the time of death. C57BL small lymphocytes were thus detectible in A/J newborns killed within 48 hr after injection, but not later. By contrast, C57BL spleen cells were readily detectible after 1, 2, and 4 days under the same conditions. When purified adult A/J small lymphocytes were injected into A/J newborns within 24 to 48 hr after injection of adult C57BL small lymphocytes, a high degree of protection from runt disease was obtainable. It is clear that circulating small lymphocytes may adoptively protect against as well as induce transplantation disease. The evidence overall indicates that immunologically competent small lymphocytes promptly attack antigenically disparate newborn hosts. These injected cells rapidly spend themselves or are eliminated by allergic injury, leaving few or no descendants with the donor antigenic constitution.