We have previously reported the protective effect of pretreatment of semiallogeneic marrow and spleen cells with Fab fragments of horse anti-mouse thymocyte globulin against otherwise 100% fatal acute graft-versus-host disease (GVHD). We have now examined the effect of this pretreatment in three allogeneic strain combinations of mice, namely, A leads to C57, CBA leads to CAF1, and CBA leads to BALB/c. Acute GVHD mortality at 15 days postirradiation and transplantation of untreated marrow and spleen cells was 100% in all the strain combinations. However, pretreatment of cells with Fab reduced acute GVHD mortality to 6, 13, and 33% for the CBA leads to CAF1, CBA leads to BALB/c, and A leads to C57 strain combinations, respectively. The combined mortality from both acute and secondary GVHD and all other causes at 60 and 200 days postirradiation was 6 and 11%, 20 and 39%, 50 and 66% for each of these strain combinations, respectively. These results provide additional evidence for the effectiveness of Fab in ameliorating acute GVHD and establish its applicability to allogeneic strain combinations.