Tracheobronchial secretions are a complex mixture of secretory fluids derived from sources within the lung. Important constituents include the mucous glycoproteins, other secretory proteins, serum proteins, lipids, salts; water makes up 95% of mucus by weight. These secretions form two phases at the epithelial surface: a mucous gel and an aqueous layer (periciliary fluid). Polymerization and aggregation of mucous glycoproteins create the gel matrix. Other macromolecules such as lysozyme, albumin, and immunoglobulin A also may participate in the process of gelation. Intermolecular forces contributing to gelation include disulfide bonding, sugar-sugar interactions between adjacent glycoproteins, and ionic interactions between the glycoprotein anionic groups (sialic acid carboxyl and sulfate) and cationic components in the secretions. Respiratory tract mucous glycoproteins are large, extended molecules, which have a high carbohydrate content. They are polydisperse, with variation occurring largely in the content of sulfated sugars and sialic acid. Factors such as cell of origin, chronic lung disease, and pharmacologic effects influence the density of these anionic (acidic) groups. Variation in acidic properties may influence the physical and virus-binding properties of mucus. Little information is available concerning the biosynthetic mechanisms in airway epithelium through which these variations are effected.