Friend virus (FV) is a complex of 2 mouse retroviruses which induce rapid erythroleukemia in many strains of adult mice. Various genes in susceptible mice can modify the outcome of FV infection. Our laboratory has identified 5 such genes including 4 major histocompatibility complex (MHC) regions (D, IA, IE and T) and one non-MHC gene, Rfv-3. These genes all influence the host immune response to FV and FV leukemia cells and can even induce spontaneous recovery from leukemia or facilitate successful protective vaccination against challenge with live FV or FV leukemia cells. This years work studied the mechanism of the influence of the MHC D region on recovery. Using mice expressing only one allele of the beta2- microglobulin gene caused a 50% reduction in the expression of the MHC D region gene product. However this did not reduce the incidence of recovery from FV leukemia indicating that heterozygous levels of the D/b allele are adequate for recovery. The results suggest that the non- recovery D/d allele or the closely linked L/d allele might cause a negative influence on the recovery process. The MHC IE region was also studied in this system, and it was found to exert both a positive and a negative influence on recovery from leukemia. The positive affect was due to the role of the E molecule on presentation of FV envelope protein antigens to the immune system. The negative effect appeared to act by its influence on selection of T cell subsets during ontogeny.