The incidences of positive anti-erythrocyte autoantibodies (AEA) in New Zealand Black (NZB), C57BL/6, their F1, F2 hybrid, and the F1 X NZB backcross mice were 100, 0, 0, 17, and 51%, respectively. This finding is in keeping with the idea that a combined effect of one to three dominant predisposing NZB gene(s) and a single dominant modifying C57BL/6 gene regulates the AEA production. Studies suggested that the modifying locus Aem-1 is loosely linked to Mup-1 locus on chromosome 4, and the gene order is Aem-1: Mup-1: Gpd-1. We analyzed the effects of the Aem-1 locus on other autoimmune traits and found that the gene action of Aem-1 is unrelated to the spontaneous productions of dsDNA-specific antibodies, the retroviral gp70-anti-gp70 immune complexes and natural thymocytotoxic autoantibodies and to the serum level of retroviral gp70. A significant association was observed between the negative AEA and the low (normal) serum IgM level in (C57BL/6 X NZB)F1 X NZB backcross mice. It remains to be determined whether the Aem-1 locus also controls the serum IgM level.