© 2010 Elsevier Ltd All rights reserved. Childhood lung disease is reaching epidemic proportions in the United States, especially in polluted urban environments. Epidemiologic studies suggest that early exposure to environmental pollutants is associated with childhood airway disease which persists into adulthood; however, the impact of lung-targeted toxicants on the respiratory system of pre- and postnatal animals is not well defined. The pattern of lung development itself may play a significant role in modulating the toxic response with significant portions of lung morphogenesis and cytodifferentiation occurring during the postnatal period. The enzyme systems responsible for bioactivation and detoxification differentiate during the perinatal period, with the majority of differentiation activity occurring for an extended period of time after birth. In addition, each enzyme system has a different pattern of differentiation during pre- and postnatal lung development. The risk of injury to a developing lung from an environmental contaminant known to target the lung in adults must be evaluated with two considerations: (1) The toxicant may have its impact by altering the processes of morphogenesis and cytodifferentiation, resulting in differential expression or organization of the lung in the adult. (2) Factors such as the stage of morphogenesis and differentiation of various subcompartments of the lungs during the time of exposure may significantly increase the severity of the toxic response. An effort must be made to separate the effects on the respiratory system produced by maternal exposure, either prior to parturition or during the suckling phase of postnatal growth, from the impacts of direct exposure on the postnatal animal. Alteration of the differentiated expression of a particular enzyme system or other functional protein by exposure during lung development, which does not lead to direct changes in lung function, may not produce adverse responses by a particular toxicant in the respiratory system.