A chronic GVH reaction induced in normal mice results in a syndrome that closely resembles SLE. In this study, we compared the autoimmune GVH syndrome induced in parent (C57BL/6Kh [B6] and B6.C-H-2bm12 [bm12]) and F1 [( B6 x bm12]F1) mice by transfer of parental spleen cells. A majority of the mice in all groups developed autoantibodies to chromatin and erythrocytes, and some of the mice also produced anti-dsDNA antibodies. The predominant isotype of the anti-chromatin autoantibodies was found to be IgG2a, although high levels of IgG2b antibodies were also present. Autoantibody production was in general more intense and more prevalent in parent----F1 hybrid combinations, compared to parent----parent infusions. No influence of host or graft gender was observed. These studies show that a chronic GVH reaction can be induced by both parent----parent and parent----hybrid combinations.