It has been proposed that uric acid is an important scavenger ofdeleterious oxygen radicals in biological systems [Ames, B. N., Cathcart, R., Schwiers, E. & Hochstein, P. (1981) ide dismutase are synthetic lethals, which are unable to complete metamorphosis under normal growth conditions. These experiments demonstrate unambiguously the importance of urate in oxygen defense in vivo and support our earlier proposal that the molybdoenzyme genetic system plays a critical role in oxygen defense in Drosophila. They also form the basis for our proposal that metamorphosis in Drosophila imposes a crisis of oxygen stress on the developing imago against which uric acid plays an important organ-specific defense. Finally, the results provide a basis for understanding the syndrome of phenotypes, including the hallmark dull brown eye color, which characterizes mutants of this classic genetic system of Drosophila.Ground-state molecular oxygen (02) is required for aerobic respiration, a process through which it normally undergoes complete tetravalent reduction to H20. However, partially reduced and highly reactive oxygen species [superoxide (O°), hydrogen peroxide, (H202), the hydroxyl radical, (OH-), and singlet oxygen (01)] are also formed as byproducts of normal aerobic metabolism and by the natural proclivity of dioxygen to abstract electrons from a variety of metabolic reactions. The biological consequences of exposure to active oxygen species originate in their reactivity with a variety of important biomolecules including nucleic acids, proteins, carbohydrates, and lipids. Many of the products of these reactions are cytotoxic, mutagenic, and carcinogenic and may be lethal to the organism. These reactions have been widely implicated in the etiology of many diseases and in the overall processes of normal cellular senescence and organismal aging (for a review, see ref.