SUMMARYAn alloantiserum (AAS) prepared in adult Brown Norway (BN) rats against Lewis (L) thoracic duct lymphocytes (TDL) exerted anti-L lymphocytotoxins and lymphoagglutinins in vitro and was capable of aborting an already developed graft-versus-host (GVH) reaction caused by L-TDL in neonatal BN rats in vivo. A blastogenic activity was not provoked by the antiserum in L lymphocytes either in vitro or in vivo. However, the AAS did promote the disappearance of L lymphocytes transfused into adult and neonatal BN animals with a higher efficiency in the adult. These observations demonstrated that the AAS did not act solely on circulating lymphocytes but also on those L cells resident in BN lymphoid tissue, because they were preferentially removed in BN animals containing “homed” radioactively labeled L lymphoid cells by lymph node reticular cells. In contrast, BN animals given antiserum prior to being transfused with L cells, and hence possessing circulating antibodies specific for the labeled allogeneic L inoculum, removed the lymphocytes very rapidly (within 2 hr or less), chiefly by action of phagocytic blood sinusoidal lining cells. Therefore, specific removal seemed to occur in animals given antiserum by whatever BN phagocytic cell the L lymphocyte had first contacted. Moreover, removal of circulating and homed cells within 24 hr in the adult and at least 36 hr in the neonatal BN animal, suggested that the antiserum penetrated into lymphoid tissue. This is in contrast to heterologous antilymphocyte serum (ALS) which had been reported not to penetrate into tissues. As transfused radioactively labeled L lymphocytes contained small cells of both newly formed and longer lived varieties, and because all labeled cells were removed by the antiserum, the AAS did not appear to affect one population of small lymphocytes in preference to another.