Neutrophils are phagocytic white blood cells that play a critical role in host defense by ingesting and killing invading pathogens. Humans and animals deficient in this oxidase suffer from recurrent bacterial and fungal infections, indicating that oxidant production by neutrophils is clinically important. The chapter reviews its uptake by neutrophils, its proposed roles in protecting neutrophils and tissue from oxidative damage, and the evidence that it affects neutrophil function and inhibits oxidative tissue injury during inflammation in humans. Bacteria and fungi stimulate neutrophils to generate oxidants, suggesting that one pathway for increasing intracellular vitamin C levels in humans might involve microbial pathogens. Vitamin C is highly water soluble and therefore cannot enter phospholipidcholesterol membranes to inhibit lipid peroxidation by directly scavenging lipid peroxyl radicals. One powerful strategy for identifying physiologically relevant antioxidants is to quantify specific oxidation products in tissues and plasma, using sensitive and specific methods such as mass spectrometry.