Small deformation oscillatory rheologic measurements have been used to investigate the structure of human and pig gastric mucus and pig duodenal mucus. All three secretions had viscoelastic properties characteristic of water-insoluble, viscoelastic gels. Mucus will flow and anneal if damaged, due to the making and breaking of its elastic structure, the measured lifetime of which was 10-120 min. Mucus reconstituted by concentration of the purified glycoprotein (pig gastric and duodenal mucus) had the same viscoelastic properties as the fresh mucus, giving evidence that the glycoprotein alone will reproduce the rheologic characteristics of the mucus. The structure of fresh mucus gel was unaffected by prolonged exposure to the following mucosal damaging agents: undiluted pig bile, 20 mM sodium taurocholate or 20 mM sodium glycocholate (all at pH 2, 6, and 8), HCl at pH 1, 2 M NaCl, and ethanol less than 40% (vol/vol). Higher concentrations of ethanol greater than 40% (vol/vol), caused dehydration and denaturation of mucus. Proteolysis by pepsin and other enzymes resulted in solubilization of the mucus gel with a complete change in the properties from an "elastic" gel to those of a "viscous" liquid. A similar collapse of mucus gel structure was observed after reduction of disulfide bonds in 0.2 M mercaptoethanol, but only after incubation for at least 50 min. This study demonstrates the stability of mucus to several mucosal damaging agents. It is proposed in vivo that although adherent gastroduodenal mucus allows penetration of these agents to the underlying mucosa, it can remain in situ and continue to protect against acid (with HCO3-) and pepsin, thus minimizing mucosal damage and maximizing repair.