Friend leukemia viru (FV) suppresses the proliferative response of normal lymphocytes to mitogens. The in vitro suppressive effect of FV on lymphocyte mitogenesis is mediated by T-suppressor cells and is under host genetic control. Lymphocytes from strains of mice of the C57BL background (e.g., C57BL/6) are resistant while cells from other strains (e.g., 129 and DBA/2) are susceptible. Genetic analyses utilizing resistant and susceptible parental strains, their F1, intercross and backcross progeny indicated that susceptibility to in vitro suppression is regulated by a single autosomal gene, dominant for susceptibility to suppression. This gene, which is not linked to the H-2 complex, segregated independently of the Fv-2 gene which controls resistance to spleen focus formation in vivo. The gene is also unlinked to the Ir-like genes which regulate the ability of H-2d mice to reject H-2b bone marrow grafts. The gene is therefore designated as Fv-3. Fv-3 may mediate its effect by regulating the numbers and/or functions of T-suppressor cells.