SUMMARY The ability to digest mucus, mucolytic activity of isolated pepsins and samples of human gastric juice has been assayed by measuring the fall in viscosity when incubated with purified pig gastric mucus glycoprotein. Pure human pepsin 1, the peptic ulcer associated pepsin, digested gastric mucus glycoprotein at a faster rate than did pure human pepsin 3 (the principal human pepsin), or the equivalent pig pepsin (pepsin A). At pH 2-0 pepsin 1 had twice the mucolytic activity of pepsin 3. Above pH 3X8 this difference became more marked and whereas pepsin 1 caused substantial mucolysis up to and including pH 5-1, pepsin 3 had minimal activity. At pH 4X0 pepsin 1 had six times the mucolytic activity of pepsin 3. Gastric juices from patients with duodenal ulcer each exhibited substantial mucolytic activity between pH 2 to 5, similar to that of pepsin 1. In contrast, gastric juice from non-symptomatic volunteers exhibited little mucolytic activity above pH 4. Analysis of the mucus glycoprotein by gel filtration showed that an increase in lower molecular weight, pepsin degraded, glycoprotein was associated with the fall in mucus viscosity for all enzyme preparations. These results showed that pepsin 1 can digest the mucus more effectively than pepsin 3 and at higher pH values. The raised concentrations of pepsin 1 in the juice of peptic ulcer patients may thus promote the ulcerative process by increased erosion of the mucus barrier under conditions likely to pertain in the duodenal bulb as well as the stomach.The mucus:bicarbonate barrier is considered to be an important component of the gastroduodenal mucosal defence mechanisms against autodigestion by the gastric juices.1-3 To function as an effective barrier the adherent mucus must be present as a continuous layer, a state maintained by a balance between its secretion from the epithelial cells and its erosion by removal from the surface into the lumen.4 Factors which swing this balance in favour of degradation of the adherent mucus might therefore be expected to decrease gastroduodenal mucosal resistance and result in mucosal damage. Agents identified in such adherent mucus erosion in vivo are proteolytic degradation and mechanical sloughing. Extensive in vitro studies show that luminal pepsins are mucolytic and dissolve adherent mucus gel by breaking down the polymeric structure