Phagocytes such as neutrophils and macrophages rapidly consume molecular oxygen upon stimulation and generate superoxide anion, which is released to the outside of the cells or inside phagosomes. This system is important for defense against microbial infection and patients with chronic granulomatous disease (CGD), whose phagocytes cannot generate superoxide anion (and hence its derivatives of other active oxygen species), suffer from recurrent, life-threatening infections with bacteria and fungi. At least five proteins are involved in the superoxide-generation in phagocytes. These are gp91-phox and p22-phox, which compose cytochrome b558 in the membrane and cytosolic p47- and p67-phox and a small molecular GTP binding protein, Rac. Any defect in the four ''phox'' proteins causes CGD. More than 200 CGD patients have been found in Japan and the incidence was calculated to be 4 - 5 in one million births. Lesions in the subunits of the cytochrome account for about 83 % of the cases and the majority of defects were found in gp91-phox, which is inherited in an X-linked fashion. Defects in other phox proteins account for 5 10%. We and others performed genetic analysis of many CGD patients, and recently we developed a drug-selectable bicistronic vector which would give higher therapeutic benefit on gene therapy of CGD patients. A complete understanding of the mechanisms of phagocyte disorders at the functional, protein and gene levels should contribute to our knowledge about primary defense mechanisms against microbial infections.