Rabeprazole is the only proton pump inhibitor that enhances the content of gastric mucin in experimental animals. We have studied, therefore, the effect of rabeprazole on the content of gastric mucin, mucus, and its viscosity in 21 asymptomatic volunteers in a double-blind study. The mucus content during rabeprazole administration significantly increased both in pentagastrin-stimulated (3.36 +/- 0.39 vs 1.50 +/- 0.32 mg/ml, P < 0.001) and basal (3.31 +/- 0.38 vs 2.28 +/- 0.36 mg/ml, P < 0.01) conditions. The content of mucin during rabeprazole was 2.6-fold (0.96 +/- 0.08 vs 0.36 +/- 0.06 mg/ml, P < 0.0001) and 41% (0.82 +/- 0.09 vs 0.58 +/- 0.09 mg/ml, P < 0.05) higher in stimulated and basal conditions, respectively. The viscosity of gastric juice during rabeprazole administration was also significantly higher both in stimulated (P < 0.01) and basal (P < 0.05) conditions. In conclusion, the unique pharmacological property of rabeprazole, significantly augmenting production of gastric mucus and mucin, may translate to additional clinical benefits in protecting the upper alimentary tract mucosa during the acid-related challenge.