The anti-leukemic effectiveness (GvL activity) and anti-host response (GvH response) of several allogeneic donor marrows were compared in lethally irradiated normal and Rauscher leukemia SJL/J recipients. Although both types of effects could be demonstrated, the degree of GvL activity did not parallel the severity of GvH response. The level of GvL activity of the donor marrow also appeared to be independent of sensitivity of the donors to the leukemia inducing Rauscher virus (RLV), as a high level of leukemia recurrence was found using marrow from RLV-resistant RF/J donors, while a lesser degree of recurrence occurred with the use of RLV-sensitive DBA-2J marrow. Analysis of the possible influence of major (MHC) and Minor (MiHL) histocompatibility loci suggested that GvL activity may be independent of the H-2 locus, and that the "a" alleles of the H-4 and H-13 loci may not be contributing to GvL effect. Likewise the "a" alleles of the H-7 and H-12 loci did not appear to affect the severity of GvH response. The possibly that GvL activity may be independent of th MHC, but governed by MiHL possibility different from those regulating GvH response might explain why in this and previous studies GvL activity could only be demonstrated following allogeneic marrow transplantation but did not appear to correlate with severity of GvH response.