After inoculation into lethally irradiated F1 mice, parental thymocytes reacting to host antigens, synthesize deoxyribonucleic acid in the spleens and lymph nodes of the recipient mice. Removal of the spleen localizing fraction of the thymocyte inoculum, by splenectomizing recipients 3 hours after cell injection, markedly alters the response of the cells in the lymph nodes without affecting the number of chromium 51 labeled cells which localize in the nodes. The effects of splenectomy may be bidirectional; increases or decreases of the lymph node response may ensue. At higher thymocyte doses splenectomy leads to an increased lymph node response, apparently by diminishing suppressive interactions among the inoculated cells. When spleen removal increases the response of the cells in the lymph nodes, reinjection of the cells removed with the spleen suppresses the response. The addition of F1 thymocytes to the inocula of parental cells can alter the response of the parental cells. Such effects of the F1 cells, which occur in the recipients lymph nodes, can be prevented by removal of the spleen localizing fraction of the thymocyte inoculum. Delaying splenectomy by 24 to 48 hr diminishes its effect. We suggest spleen localizing T cells may play an important role in immuno-regulation.