The effect of bile acids on the glycoprotein constituent of gastric mucus was investigated. Ghosh-Lai rat stomachs were instilled in vivo for 1 h with buffered saline (control) followed by various bile acids in saline at pH 2.0-7.0. Following quantitative recovery, the instillates were used for the isolation of mucus glycoprotein. The results of analyses revealed that while taurocholic acid exerted essentially identical depletory effects throughout the entire pH range tested, the cholic acid had little depletory effect on the mucus below pH 5.0, and glycocholic acid below pH 4.0. The extent of mucus glycoprotein depletion by bile acids under optimal pH conditions was clearly dependent upon the bile acid concentration as well as its type. The maximum depletory effect with the lowest concentration of bile acid was achieved with taurocholate followed by glycocholate and cholate. Comparison of the depletory effects of mono-, di-, and trihydroxy conjugated and unconjugated bile acids revealed that, within each group, the highest degree of mucus glycoprotein depletion occurred with taurine conjugates. The number of hydroxyl groups on the bile acid molecule appears to exert a less evident effect on the depletory capacity. The results suggest that the in vivo depletion of gastric mucus of its glycoprotein constituent by bile acids depends on the pH of luminal exposure and on the bile acid composition.