SUMMARYUnder in vitro conditions, spleen cells from Fx hybrid mice undergoing graft-versus-host (GVH) reactions exerted a nonspecific cytotoxic effect upon target cells of syngeneic, allogeneic, or xenogeneic genotype to the parental strain. The cytotoxic effect was dependent on the intensity of GVH reactions and necessitated direct contact between target cells and metabolically active spleen cells; no lysis could be induced with the cell-free supernatant of cultures of these spleen cells