The canine gastric response to acute dilatation, its correlation with selected systemic cardiovascular changes, and preliminary study of its modulation by membrane-stabilizing agents were studied in 21 Beagle dogs. Gastric mucosal damage and adverse cardiovascular sequelae were induced by inflation of an intragastric balloon to 60 mm of Hg in each anesthetized dog for 2.5 hours. At this time, dogs were given 1 of 4 treatments: control; lidocaine HCl, 2.2 mg bolus + 66 micrograms/min, IV; prednisolone succinate, 6.6 mg, IV; and zinc sulfate, 2.2 mg bolus + 66 micrograms/min, IV. After treatments were given, there was a 4-hour deflation period. Throughout the 6.5 hours, continuous measurements were made of stroke volume, arterial blood pressure, PaO2, PaCO2, and plasma HCO3- concentration. Gastric lesions, assessed by planimetric analysis of ulcer indices, were limited to the fundus and corpus and were significantly decreased by lidocaine administration. As seen by histopathologic examination, a sharply delineated transverse area bordering the corporeal-antral junction near the lesser curvature demonstrated minimal resistance to ulceration and showed mucus depletion. Plasma HCO3- concentration, base excess, and CO2 values were negatively correlated with development of gastric damage, indicating that plasma HCO3- concentration has a key role in mucosal resistance to ulcerogenesis.