Antibody and rejection responses against the Moloney leukemia virus-induced YAC lymphoma of A strain origin were found to be weak in A but high in (A×C57Bl)F₁ hybrids. (A×C57Bl) × A backcross mice typed for expression of H-2 antigens were investigated for these responses in order to ascertain the importance of the H-2 phenotype of the host and the development of antibodies for rejection of the tumor cells. With an LD₅₀ challenge inoculum in immunized backcross mice, the presence of anti-YAC antibodies appeared to be important for protection against the outgrowth of the tumor, particularly in the H-2^a mice. None of them survived, unless antibody-positive. On the other hand, a proportion of the H-2 heterozygous mice rejected the tumor in the absence of antibodies. In the antibody-positive group a higher number of H-2 heterozygous mice survived than of H-2 homozygous mice. The results showed that both humoral and cellular responses are important for the rejection of an antigenic lymphoma and indicate the contribution of an F₁ anti-parental component in the latter.