© 2004 Elsevier Ltd All rights reserved.. This chapter describes the pattern of differentiation for antioxidant enzyme pathways as well as bioactivation detoxification enzyme systems during pre- and postnatal lung development. During both the pre- and postnatal period of lung development, there are rapid rates of cellular differentiation, cell division, and alveolarization occurring, making the early postnatal lung uniquely susceptible to injury by environmental oxidant and toxic air pollutants. The enzyme systems responsible for protection from oxidant injury and toxicant-induced injury differentiate during the perinatal period, with the majority of differentiation activity occurring for an extended period of time after birth. Each of these enzyme systems is expressed in a different pattern during pre- and postnatal lung development. Antioxidants and antioxidant enzymes protect the lung from oxidant pollutants such as ozone and nitrogen dioxide. Xenobiotic metabolizing enzymes act on compounds to make them more water-soluble and increase their rate of elimination. In general, the pulmonary antioxidant enzyme system develops during the last 10-15% of gestation in humans as well as in laboratory animals such as rats, hamsters, guinea pigs, rabbits, and lambs. CYP monooxygenases are expressed later during lung development, suggesting a role in protecting the lung from exogenous, rather than endogenous, compounds.