The Wiskott-Aldrich syndrome is an X-linked immunodeficiency disorder consisting of the triad of frequent infections, eczema, and profound thrombocytopenia. We evaluated the effects of splenectomy on hemostatic improvement and subsequent clinical course in 16 patients with the Wiskott-Aldrich syndrome. All 16 had an increase in platelet counts to at least 100,000 per cubic millimeter after splenectomy, with the mean increasing from 19,900 per cubic millimeter preoperatively to 262,700 per cubic millimeter after splenectomy. In addition, platelet size, which is characteristically small in this disease, also became normal. Survival after splenectomy correlated with the prophylactic use of antibiotics. Five of seven patients not taking prophylactic antibiotics died of sepis within 33 months of surgery. The mean survival of the nine patients maintained with prophylactic antibiotics, however, was at least 91.4 months, with six of these patients still alive an average of 11.0 years or more after splenectomy. Thus, splenectomy is a useful therapy for a major cause of morbidity and mortality in this complex syndrome.