Mouse and human monoclonal autoantibodies have been prepared from the spleens of virus-infected animals and from the peripheral leukocytes of patients with diabetes mellitus. A number of these antibodies have been found to react with antigens in more than one organ and are referred to as multiple organ reactive (MOR) antibodies. For example, some of the human MOR antibodies react with antigens in the pituitary, thyroid, pancreas, and stomach. By using antibody affinity columns, some of the autoantigens with which MOR antibodies react have been isolated and their molecular weights determined. The results suggest that MOR antibodies react either with the same molecule present in same several organs or with common antigenic determinants on different molecules in multiple organs. MOR antibodies may be a partial explanation from multiple organ autoimmunity.