Autoimmune Neutropenia of Infancy (ANI) is generally regarded as a benign condition diagnosed by finding neutropenia and a positive test for antineutrophil antibodies. To determine whether the presence of antineutrophil antibodies in infancy always predicts a benign disease, data were reviewed for young children with positive antineutrophil tests who are enrolled in the Severe Chronic Neutropenia International Registry (SCNIR). A set of identical twins presented with severe neutropenia at age 5 months. Twin A1 had a preceding history of aphthous ulcers, cellulitis, recurrent otitis media, pneumonitis, an episode of bacteremia and a positive test for antineutrophil antibodies<INS cite=mailto:%20 dateTime=2005-08-01T10:53>.</INS> Twin A2 had a preceding history of cellulitis, otitis media, and pneumonitis. The median absolute neutrophil count (ANC) of twin A1 and twin A2 was 0.280 x 109/L and 0.116 x 109/L, respectfully and bone marrow examination for twin A1 showed maturation arrest at the myelocyte-metamyelocyte level. With the diagnosis of ANI in one twin, both twins were placed on granulocyte-colony stimulating factor (G-CSF), because of frequent fever and recurrent infections. Fifty-one months after the diagnosis of immune neutropenia, twin A1 developed acute myelogenous leukemia. Further studies then revealed that both twins had a mutation in the neutrophil elastase gene (ELA2) at exon 5 resulting in a nucleotide substitution from TGC to TGA, which indicated a diagnosis of severe congenital neutropenia. Another set of fraternal twins were identified to have ANI at six months because of recurrent abscesses, mouth ulcers, otitis media and positive tests for antineutrophil antibodies. The ANC was 0.067 x 109/L in twin B1 and 0.166 x 109/L in twin B2. At age 31 months twin B1 developed a severe Clostridial infection, which led to the loss of his right leg and part of the anterior abdominal wall. Subsequently both twins were placed on G-CSF. Prior to G-CSF treatment, bone marrow studies revealed an arrest at the promyelocyte stage and an ELA2 mutation in exon 4 leading to a TCG to TTG substitution in both twins thereby indicating a diagnosis of severe congenital neutropenia. Upon further review of the SCNIR, eight other congenital patients were identified to have antineutrophil antibodies and bone marrow patterns consistent with severe congenital neutropenia. In conclusion, it is important to be aware that positive antineutrophil antibodies can occur associated with severe congenital neutropenia. Infants with severe neutropenia and repeated or severe bacterial infections should have a bone marrow examination and ELA2 evaluation to establish correctly the underlying pathogenesis of the neutropenia.