Background The hyper-IgE syndrome is a primary immunodeficiency characterized by severe recurrent abscesses, pneumonia with pneumatocele formation, and elevated serum IgE. Eosinophilia, neutrophil chemotactic defects, and marked tissue damage are frequently present in this syndrome. Objective To study whether functional changes in cytokines, adhesion molecules, and neutrophils might help explain these clinical observations. Methods The following functions were analyzed in patients with the hyper-IgE syndrome and in controls: (1) production of granulocyte-macrophage-colony-stimulating factor by peripheral blood mononuclear cells by ELISA; (2) respiratory burst and reactive oxygen intermediates production by peripheral neutrophils using the luminol-enhanced chemiluminescense technique; and (3) expression of l-selectin on granulocytes and lymphocytes by flow cytometry. Results Patients with hyper-IgE syndrome had significantly increased production of granulocyte-macrophage-colony-stimulating factor by resting or stimulated mononuclear cells, increased generation of reactive oxygen intermediates by neutrophils treated with opsonized zymosan, and reduced l-selectin expression on quiescent and activated granulocytes and lymphocytes. Conclusions Our results suggest that an important feature of the hyper-IgE syndrome is the increased production of granulocyte-macrophage-colony-stimulating factor, which may explain the reduced l-selectin expression, decreased chemotaxis, and increased oxygen radical production and tissue damage in this disease.