This investigation is concerned with the influence of the major histocompatibility complex (H-2) on susceptibility of mice to mouse mammary tumor virus (MuMTV). Various strains of mice congenic for the H-2 complex with a C57BL/10 or BALB/c background have been selected for testing. Preliminary studies with these congenics have established that they do not express MuMTV in their milks and that although low levels of MuMTV RNA can be detected in lactating mammary glands, no significant differences exist in the expression of endogenous MuMTV information. These strains of congenic mice are being inoculated with MuMTV from various sources. The concentrations of virions in the inocula are quantitated by nucleic acid hybridization assay. Virus replication in the infected hosts is being measured by radioimmunoassay for gp55, the major virus glycoprotein, in the milks of third lactation mice, and mice are also being observed for incidence of mammary tumors. These data should establish the influence of the H-2 complex on MuMTV susceptibility and the location of the gene(s) involved. In addition, techniques are being developed to study the cellular and humoral immune responses of these mice to virus antigens in order to elucidate the mechanisms involved in H-2 determined susceptibility to a virus-associated carcinoma.