The influence of the Ipr gene on the anti-DNA antibody response was investigated in MRL and B6 Ipr/Ipr inbred mice, MRL +/+ mice less than a yr of age produced low levels of anti-DNA antibody, whereas older animals of this strain demonstrated levels in some instances comparable to those of the more severely affected MRL Ipr/Ipr mice. This result indicates a tendency to autoreactivity in MRL mice independent of the Ipr gene. To determine whether other mice bearing the Ipr gene would also express autoantibodies, the anti-DNA antibody responses of B6 Ipr/Ipr mice were studied. This strain was development by matings to transfer the Ipr gene into another inbred background and allow evaluation of the action independent of other disturbances of the MRL mice. Mice of this strain produced antibodies to DNA, with female animals displaying significantly higher levels than males. This result demonstrates that the Ipr gene can stimulate autoantibody production in mice other than the MRL strain and does not require abnormalities unique to this background to potentiate autoreactivity.