Using as a model the lethally irradiated mouse restored with allogeneic bone marrow from which particular Lyt and Lyb subsets have been serologically eliminated, with or without prior induction by lymphocyte precursors, we propose to determine the conditions under which immunologically competent chimeras free of GvH disease can be constituted. Our approach is based on the recognition that different, functionally-distinct subpopulations of lymphocytes can be distinguished and separated on the basis of their immunogenetic surface phenotypes. It also recognizes that agents such as thymopoietin and ubiquitin may induce committed lymphocyte precursors to express surface components characteristic of differentiated cells, and that these cells can then be eliminated by antiserum identifying lymphocyte subclasses. Lethally irradiated CBA/J mice will be reconstituted with bone marrow from syngeneic (CBA/J), allogeneic H-2-incompatible (C57BL/6), or allogeneic H-2 compatible (congenic C57BL/6.H-2k) donors. (CBA X C57BL/6)F1 hybrids will also be used as bone marrow recipients to control for the contribution of HvG reactivity. Bone marrow will be transplanted either untreated, or after serological elimination of particular Lyt and Lyb subsets, with or without prior induction of lymphocyte precursors with thymopoietin or ubiquitin. Mice so reconstituted will be compared for: 1) the severity of GvH reaction; 2) the restoration pattern of H-2-positive cells and of Lyt subpopulations in the spleen and lymph nodes; and 3) evidence of immunocompetence, measured by standard functional tests. Other studies will be performed to assess the effect of subpopulation elimination on the proliferative and differentiative capacity of hematopoietic stem cells and committed precursor cells, both in the donor marrow and in the reconstituted host.