Frog fundic mucosas mounted in Ussing chambers between HCO-3-buffered nutrient and unbuffered secretory solutions were exposed to 1 M NaCl on the mucosal surface for 10 min. After washing and return to control solutions, transmucosal potential difference, short-circuit current, and tissue electrical resistance decreased markedly, but within 6 h these measurements had gradually returned to almost control values. A net luminal alkalinization occurred during the first 4 hours, changing into a net acid secretion of approximately 1.1 mumol . cm-2 . h-1 at 6 h. Histamine increased H+ secretion in all tissues at 8 h. In seven metiamide-treated tissues, an average alkaline flux of approximately 0.75 mumol . cm-2 . h-1 was obtained during the first 4 h after damage, decreasing to approximately 0. 40 mumol . cm-2 . h-1 during the ensuing 4 h. With HCO-3-free nutrient solution (n = 7) luminal alkalinization was decreased by about 80% 2-4 h after injury. After 1 M NaCl, the surface epithelium and gastric pit cells were destroyed and partially lifted from the gastric glands. The lamina propria between the remaining intact glands was open to the lumen or contiguous with the damaged mass of cells and mucus. During the 6 h after damage, there was a gradual process of restitution of epithelial integrity, beginning with squamous-shaped cells that appeared to be migrating from the glands and ultimately concluding with complete epithelialization by cuboidal and columnar cells. Typical junctional complexes were present between adjacent epithelial cells. The uniformity of the restoration process was such that it was possible to predict blindly in toluidine blue-stained semithin sections whether the recovery stage was short (30 min or less), intermediate (1-2 h), or advanced (4-6 h). These observations indicate that there is a very intimate correlation between the restoration of epithelial continuity and the reestablishment of secretory and electrical activity of frog gastric mucosa damaged by hypertonic NaCl in Ussing chambers.