Wiskott, in 1937, described three brothers who presented shortly after birth with thrombocytopenia, bloody diarrhea, eczema, and recurrent ear infections [104]. Subsequently, Aldrich observed a family with multiple affected males, clearly demonstrating the X-linked mode of inheritance of this syndrome [1]. Following these early descriptive reports of the Wiskott-Aldrich syndrome (WAS), attention was directed towards assessment of the immune system and platelet abnormalities. In 1968, two reports addressed in detail the immune defect of WAS [10, 18]. Characteristic abnormalities included lymphopenia, lymphocyte depletion in the thymus and T-dependent pericortical areas of lymph nodes, defective delayed-type hypersensitivity, lack of isohemagglutinins, and failure to produce antibodies to polysaccharides and to a variety of bacterial protein, and viral antigens. The consistent platelet abnormalities were explained by increased destruction of defective platelets [7, 37, 66] or, alternatively, by ineffective thrombocytopoiesis [47, 70, 76]. The finding of eosinophilia, multiple food allergies, and elevated IgE levels suggested an allergic basis for the eczema [9]. An increased risk of malignancies, including lymphoma, malignant reticuloendotheliosis, and leukemia, was reported as early as 1961 [42, 97, 99]. Distinguishable from the classic WAS phenotype (MIM 301000) is a milder form designated as hereditary X-linked thrombocytopenia (XLT, MIM 313900)[15, 16, 69, 95]. The genes for both WAS and XLT have been mapped to Xpl 1.22 [26, 51] and sequence analysis has identified mutations of the same gene in both phenotypes [22, 101]. The gene coding for the WAS protein (WASP) is composed of 12 exons containing 1,823 base pairs and encodes a 502-amino acid protein [22]. WASP, localized predominantly in the cytoplasm [82] appears to be of central importance for the function of hematopoietic cells and is expressed in all hematopoietic stem cell-derived lineages [108]. Although the precise function of WASP is unknown, several unique binding domains have been identified. Considering the function of these domains, WASP appears to play a critical role in signal transduction by interacting with SH3-containing molecules and in the regulation of the cytoskeletal reorganization, which is necessary for the polarization of T cells during contact with antigen-presenting cells [96]. The identification of the WASP gene has had an impact on establishing the diagnosis of WAS on a molecular basis, on carrier detection and prenatal diagnosis. Treatment is largely symptomatic and includes antibiotics, prophylactic intravenous ira-