Evolution of vertebrates from aquatic medium to the terrestrial atmosphere containing high concentration of environmental oxygen was accompanied by tissue-specific expression of the gene for L-gulonolactone oxidase (LGO). LGO is the terminal enzyme in the pathway of biosynthesis of ascorbic acid in animals. In this paper we present data to indicate that emergence of LGO is apparently to provide the terrestrial vertebrates with adequate amount of ascorbic acid and thereby protect their tissues against oxygen toxicity. Superoxide dismutase (SOD) was not induced in the early tetrapods. However, SOD activity has increased in the mammals which is accompanied by a decrease in the LGO activity. In fact, there has been an inverse relationship between LGO and SOD in the progress of evolution. SOD activity is markedly high in the guinea pig, flying mammal, monkey and man, the species those lack LGO. The inverse relationship between LGO and SOD is also observed in rats during postnatal development, that is when the new born rats are exposed to high concentration of atmospheric oxygen. Recent results from our laboratory indicate that ascorbic acid is specifically needed for protection of microsomal membranes against cytochrome P450-mediated lipid peroxidation and protein oxidation, where SOD is ineffective. Data presented in this paper also indicate an apparent tissue-specific correlation among LGO activity, P450 level and O2.- production during phylogenetic evolution.