BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) can be associated with various disorders. However, their association with neutropenia has never been reported. METHODS: Nine patients with chronic unexplained neutropenia and ANCA were studied. Clinical charts were extensively analyzed and all patients underwent hematological and immunological investigations. RESULTS: All patients (6 women and 3 men) were Caucasian and had a mean age of 49 years (range 16-67 years). All presented with a neutropenia below 1.5x10(9)/L for more than 6 months. The neutropenia was <0.5x10(9)/L in six cases and moderate in three. There was no evidence of toxic- or drug-related neutropenia or of a hematological malignancy. Autoimmune anemia and/or thrombocytopenia were present in five patients. ANCA, with various specificities, were present in all patients. ANCA were associated with various other autoantibodies in eight patients, including antisurface-neutrophil antibodies in three cases. Four of the six patients with severe neutropenia experienced infections. Five patients were treated with hematopoietic growth factors, steroids, intravenous immunoglobulins, splenectomy, methotrexate and/or cyclophosphamide, allowing the neutrophil count to be restored transiently or permanently. CONCLUSIONS: A subset of patients with neutropenia of possible autoimmune origin may develop ANCA. Their detection would provide strong evidence of an autoimmune mechanism. Neutropenia should be added to the list of ANCA-associated diseases.