The genetic control of the primary and secondary IgG responses to sheep erythrocytes has been studied by using inbred, H-2-congenic, and intra-H-2-recombinant mouse strains. According to our results, the primary IgG respone is under multigenic control. There is a correlation, however, between the titer of primary IgG antibodies produced and the H-2 phenotypes among the mouse strains tested. One H-2-linked gene maps at the I-B subregion, whereas another gene can be mapped at or closely linked to the H-2D region. Low and high responsiveness were associated with H-2b, H-2f and H2a, H-2d, H-2k phenotypes, respectively. By comparison of the responses of inbred and congenic strains having the same H-2 phenotype, it can be concluded that background genes influence the primary response only slightly but have almost complete control over the secondary response.