Genes that control expression of retroviruses are being studied in three strains of mice: B10.AKM, NZB and HRS. In the B10.AKM congenic system there is high grade expression of B-tropic C type RNA virus and a high incidence of reticulum cell sarcoma. Both events appear to be related to loci within the H-2 complex. In the NZB mouse two genes specify expression of xenotropic virus; investigations of how these genes are related to disease in this strain are in progress. The HRS strain carries an autosomal recessive mutant gene, hr, which specifies high grade expression of a xenotropic virus. The mutant also has a high incidence of thymic lymphoma. The relation between xenotropic virus, ecotropic viruses and a possible recombinant between the two agents to the lymphoma is being investigated.