Sera of patients with systemic lupus erythematosus were demonstrated to contain precipitating antibodies to soluble tissue components other than DNA. One dominant reaction was observed which was provisionally termed the Sm system. The antigen involved was identified in nuclei of a wide variety of cells from different species. It was associated with protein fractions but was a non-histone substance quite sensitive to periodate treatment. Antibodies to the Sm antigen could also be detected by complement fixation. They showed a high incidence in systemic lupus erythematosus with considerable specificity for the disease.