Exogenous administration of substances extracted from rodent salivary glands may increase the resistance of gastric mucosal barrier to the disruptive actions of ulcerogenic agents and/or reduce acid secretory output. In the present study the influence of desalivation in the rat on acid secretory function and mucosal integrity has been investigated. Experiments were performed on rats 4 wk after removal of the major salivary glands and ligation of the salivary ducts. Intravenous infusion of pentagastrin (0.1--0.4 microgram/kg/min) resulted in an increase in acid output in desalivated rats although the responses was less than that observed in sham-operated controls. Intraluminal instillation of a bile salt solution (5 mM in 150 mM HCl) in control animals resulted in a significant loss of H+ and the luminal appearance of Na+ and K+. The net fluxes of Na+ and K+ were exacerbated in the desalivated group. Furthermore, the mean area of bile salt-induced ulceration was significantly greater in desalivated rats than in the control group. In the absence of bile salt treatment there was no difference in either the transmural ionic fluxes or area of ulceration between the two groups. These results suggests that removal of the major salivary glands in rats decreases the resistance of the gastric mucosa to bile salt-induced damage.