Evidence is reviewed supporting the view that vitamin A (retinol) and its metabolite, retinoic acid, called natural retinoids, are major factors involved in differentiation and in maturation of the lungs. This conclusion is based on morphological observation that lack of this dietary micronutrient causes keratinizing squamous metaplasia of the bronchopulmonary tree that can be reversed by refeeding the animal with retinol. In addition to these observations suggesting an indirect participation of retinol and/or retinoic acid in the differentiation of this organ, more direct evidence is presented that this vitamin is involved in pulmonary gene expression. Adult as well as fetal lungs accumulate retinyl esters, the storage form of vitamin A, contain specific retinol- and retinoic acid-binding proteins and, more importantly, express several isoforms of nuclear retinoic acid receptors. These proteins are involved in activation and repression of specific genes regulated by retinoic acid. That retinol and/or retinoic acid may be involved in lung maturation is suggested by experimental results showing depletion of lung retinyl esters at birth, by significant alterations in the levels of the cellular retinoic acid-binding protein during lung maturation and, more importantly, by reduction in the morbidity of prematurely born human neonates who are given vitamin A because they are susceptible to bronchopulmonary dysplasia.