Organ allografts survive in hosts treated with immunosuppressive drugs. The question arises as to whether cells isolated from organ or tissue of an allogeneic donor and transplanted to a genetically disparate recipient can also benefit from the immunosuppressive regimen. We reported previously that the DST (donor specific transfusion) recipients accept heart allografts but reject hyperacutely i.v. infused lymphocytes from the same as DST donor. The present study was devoted to elucidation of the mechanism of these divergent processes. Syngeneic BN hearts and mesenteric lymph node lymphocytes were transplanted to LEW rats pretreated one week previously with donor specific blood transfusions. The allogeneic BN lymphocytes transplanted i.v. to LEW rats receiving one BN DST were rejected hyperacutely within 6 hrs, whereas BN heart grafts transplanted to the BN DST-treated LEW recipients survived 14 +/- 2 days. Adoptive transfer of LEW anti-BN DST sera to naive LEW rats caused destruction of the transplanted BN lymphocytes. The LEW BN DST recipients possessed IgG and IgM class alloantibodies binding to BN lymphocytes and heart endothelial cells. mAbs against MHC class I (OX18) and class II (OX6) antigens neither blocked binding of antibodies of DST-recipient sera to BN lymphocytes nor protected the preincubated BN lymphocytes against destruction after transplantation. Western blot analysis revealed that alloantibodies from DST-recipient sera bound strongly to BN lymphocyte membrane proteins of 60 kd m.w. but not to 45 kd and 30 kd MHC class I and II proteins. Taken together, DST has no protective effect on intravenously transplanted cells. In contrast, it accelerates the rejection. Alloantibodies present in DST-recipient sera "shield" antigens on the surface of organ allograft endothelial cells, thereby protecting them from recognition and cytotoxic effect. Simultaneously, these alloantibodies "opsonize" the intravenously transplanted lymphocytes and facilitate their halting in lymphoid organs and subsequent lysis. Antibodies other than those directed against MHC seem to mediate both these processes. The results of these studies provide also evidence that the effector mechanism of rejection may be different depending on location of the graft, in the lymphoid as in case of transplanted lymphocytes or in non-lymphoid tissues as heart grafts.