Superoxide production via NADPH oxidase has been shown to play a role in neurotoxicity, ischemic stroke, and possibly Parkinson's and Alzheimer's diseases. In addition, NADPH oxidase-dependent production of superoxide may be necessary for normal brain functions, including neuronal differentiation and neuronal plasticity. To improve our understanding of NADPH oxidase in the brain, we studied the localization of the various protein components of NADPH oxidase in the central nervous system of the adult mouse using immunohistochemistry. We detected staining for the cytoplasmic NADPH proteins, p40(phox), p47(phox), and p67(phox), as well as the membrane-associated NADPH oxidase proteins, p22(phox) and gp91(phox) in neurons throughout the mouse brain. Staining of each of the NADPH oxidase proteins was observed in neurons in all regions of the neuraxis, with particularly prominent localizations in the hippocampus, cortex, amygdala, striatum, and thalamus. The expression of NADPH oxidase proteins in neurons suggests the possibility that enzymatic production of superoxide by a NADPH oxidase may play a role in both normal neuronal function as well as neurodegeneration in the brain.