Autoimmune-mediated cell destruction in peripheral blood has been considered the most frequent cause of cytopenias seen in systemic lupus erythematosus. On the other hand, several bone marrow abnormalities have been documented by case reports as well as retrospective studies. In the present prospective analysis we addressed the question of the frequency and features of bone marrow abnormalities in SLE patients presenting peripheral blood cytopenias. In 12 of the 21 patients examined, we found foci of an exudative necrotic reaction characterized by edema, necrotic cells (nucleophagocytosis) and an infiltrate by lymphocytes, plasma cells and macrophages. Reticulin fibers were increased in these foci in 8 cases. Surprisingly, hemopoiesis was hyperplastic in only 6 patients, but was grossly diminished in 12 cases. In 14 patients atypical elements of one or more cell lines could be observed. Most commonly (11 cases), an increase in megakaryocytes with atypical elements showing small pleomorphic nuclei could be seen, together with normal nuclei. Cell atypia in the erythroid line was found in 8 cases, and abnormal granulocytic precursors were seen in 3 cases. No ring sideroblasts could be observed in any case. All these features provide persuasive evidence that the bone marrow is a common target organ affected by autoaggression in SLE. Central and peripheral mechanisms acting to produce peripheral cytopenias must be assumed in most cases.