This study was conducted to determine whether taurocholate alters human gastric function and structure at a neutral pH, when ionized, and to contrast this with its effect at an acid intraluminal pH, when pronated. Five fasted healthy subjects were studied on 4 days in random order. Net ion fluxes, mucosal damage (as quantitated endoscopically), and potential difference were measured. The control solution instilled into the stomach in the first, third, and fourth 15-min periods contained 200 ml of 100 mM HCl, 54 mM mannitol, and [14C]polyethylene glycol. Taurocholate (10 mM) was added to the control solution (pH 1.1) or citrate buffer (pH 7.0) during the second 15-min period. The effect of citrate buffer alone or control solution alone was also tested. Because hydrogen and sodium fluxes could not be quantitated at pH 7 in the presence of citrate buffer, the net ion fluxes during the 15 min immediately after exposure to the test agent were measured. At both pH 1.1 and 7.0 taurocholate produced similar and significant increases in net hydrogen ion flux (-1.7 +/- 0.4 and -1.8 +/- 0.3 mmol/15 min, respectively), net sodium ion flux (1.8 +/- 0.4 and 1.7 +/- 0.2 mmol/15 min, respectively), decreases in potential difference, and mucosal erosions. The net hydrogen ion fluxes were significantly greater than occurred after citrate buffer alone or the HCl control. The net sodium fluxes after taurocholate in citrate were significantly greater than the pH 1.1 acid control, but not citrate buffer alone. These findings indicate that pronated (pH 1.1) or ionized (pH 7.0) taurocholate significantly damaged the in vivo human gastric mucosa. Taurocholate at pH 7 could in part be responsible for the gastric mucosal injury that occurs in patients with bile reflux gastritis.