Patients with selective IgG2 subclass deficiency (IgG2 SD) usually suffer from recurrent respiratory infections. The occurrence of cytopenia is extremely rare in these patients. We report on two patients with isolated IgG2 SD who experienced unexplained severe neutropenia associated with T-lymphocyte proliferation. IgG2 SD clearly preceded the occurrence of neutropenia in one patient. In the other patient, the long-standing history of recurrent respiratory infections prior to diagnosis of agranulocytosis suggests that IgG2 SD also preceded the occurrence of neutropenia. Analysis of bone marrow biopsy in both patients and skin tissue lesions in one patient showed massive infiltration with CD4+ and CD8+ T-lymphocytes. The pathological feature did not suggest any malignant lymphoproliferative disorder. Neutropenia was refractory to i.v. Ig in both patients and to recombinant G-CSF, steroids, and cyclophosphamide in one patient. Severe cellulitis led to death in one patient. In summary, we reported herein a heretofore undescribed syndrome characterized by the association of IgG2 SD with severe neutropenia and tissue T-cell infiltration. It suggests that bone marrow analysis as well as determination of serum IgG subclasses need to be performed in patients with unexplained neutropenia.