The airway mucosa is lined by a continuous epithelium comprised of multiple cell phenotypes, several of which are secretory. Secretions produced by these cells mix with a variety of macromolecules, ions and water to form a respiratory tract fluid that protects the more distal airways and alveoli from injury and infection. The present article highlights the structure of the mucosa, particularly its secretory cells, gives a synopsis of the structure of mucus, and provides new information on the localization of mucin (MUC) genes that determine the peptide sequence of the protein backbone of the glycoproteins, which are a major component of mucus. Airway secretory cells comprise the mucous, serous, Clara and dense-core granulated cells of the surface epithelium, and the mucous and serous acinar cells of the submucosal glands. Several transitional phenotypes may be found, especially during irritation or disease. Respiratory tract mucins constitute a heterogeneous group of high molecular weight, polydisperse richly glycosylated molecules: both secreted and membrane-associated forms of mucin are found. Several mucin (MUC) genes encoding the protein core of mucin have been identified. We demonstrate the localization of MUC gene expression to a number of distinct cell types and their upregulation both in response to experimentally administered lipopolysaccharide and cystic fibrosis.