Routine examination of sera from patients with suspected or confirmed connective tissue disease has revealed the presence of autoantibodies directed against an unusual nuclear antigen. As characterized by immunofluorescence studies, the antigen is found exclusively in the nuclei of interphase cells, but appears to be part of the spindle pole in mitotic cells. Similar distributions in interphase and mitotic cells have been reported for the recently discovered nuclear mitotic apparatus (NuMA) protein. Using immunoblot analysis we have demonstrated that the autoantibodies that decorate the mitotic spindle poles are specific for the NuMA protein. Therefore, we conclude that the NuMA protein is a human autoantigen.