In addition to the pyridine nucleotide binding site homology sequence, data from ours and from other laboratories indicate that the cytochrome binds FAD and its analogs, and contains two hemes for each FAD. Early studies missed the presence of FAD due to the inability to recover FAD after detergent extraction, but the flavin can be reconstituted in the presence of phospholipids. Thus, the cytochrome contains all of the known redox centers of the respiratory burst oxidase. A model of the large subunit can be constructed based on a combination of hydropathy analysis and available information regarding homology of N-terminal regions with heme binding regions of known hemoproteins as well as homology with known flavoprotein dehydrogenases. According to this model, the very hydrophobic N terminal 225 or so amino acids loops back and forth across the plasma membrane at least 5 times. This region also contains the two hemes (light red structures), which we suggest lie in a transmembrane arrangement. The C-terminal two thirds of the molecule contains the homology regions for NADPH and FAD binding, and is proposed to fold into a globular domain analogous to known flavoprotein dehydrogenases.