Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder which is manifest by complement-mediated hemolysis, venous thrombosis, and bone marrow failure. Complement-mediated hemolysis in PNH is explained by the deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59 on erythrocyte surfaces. All the PNH patients had phosphatidylinositol glycan-class A (PIG-A) gene abnormalities in various cell types, indicating that PIG-A gene mutations cause the defects in GPI-anchored proteins that are essential for the pathogenesis of PNH. In addition, a PIG-A gene abnormality results in a PNH clone. Bone marrow failure causes cytopenias associated with a proliferative decrease of its hematopoietic stem cells and appears to be related to a pre-leukemic state. Although it is unclear how a PNH clone expands in bone marrow, it is considered that the most important hypothesis implicates negative selection of a PNH clone, but it does not explain the changes in the clinical features at the terminal stage of PNH. Recently, it has been suggested that an immune mechanism, in an HLA-restricted manner, plays an important role in the occurrence or selection of a PNH clone and GPI may be a target for cytotoxic-T lymphocytes. Also, it has been indicated that the Wilms' tumor gene (WT1) product is related to a PNH clone, but the significance of WT1 expression is not clear because of the functional diversity of the gene. To elucidate this problem, it is important to know the pathophysiology of bone marrow failure in detail and how bone marrow failure affects hematopoietic stem cells and immune mechanisms in bone marrow failure syndromes.