The humoral immune response to Friend virus leukemia was studied in congenic F1 mice differing in their incidence of recovery from leukemia. Antiviral neutralizing antibodies rose in titer in vivo concurrently with disappearance of viremia and fall in spleen virus levels. Cytotoxic antileukemia cell antibodies also appeared at this time. Passive transfer of these antibodies could inactivate low numbers of leukemia cells in vivo; however, mice of both high and low recovery genotypes produced antibodies in equal titer and recovered from viral infection in spite of striking differences in recovery from leukemic splenomegaly. Mice lacking C57BL genes did not produce antibodies or recover from viremia except in rare instances. Recovery from splenomegaly was found to be influenced by three or more C57BL genes independent of the H-2 complex.