AbstractThe microbicidal oxidase of phagocytes, upon activation, reduces molecular oxygen to superoxide in conjunction with the oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH). The terminal component of the oxidative cascade is cytochromeb558consisting of 91 kDa (gp91‐phox) and 22 kDa (p22‐phox) subunits with heme acting as the electron carrier to oxygen. However, the NADPH‐binding flavoprotein that transports electrons from the substrate to the cytochrome has not been identified. Alignment of the amino acid sequence of gp91‐phoxwith that of previously characterized flavoproteins suggests that this subunit contains both the NADPH‐and flavin adenine dinucleotide (FAD)‐binding domains. Several lines of experimental evidence strongly support this proposal. Thus cytochromeb558is regarded as the first example of a flavocytochrome in higher eukaryotes, comprising the complete electron transporting machinery of phagocyte NA