An unusual sudden potential drop (SPD) has been described by Kidder in bullfrog gastric mucosa exposed to anoxia and a serosal pH less than or equal to 7.1. We found that anoxia was not a prerequisite, since under fully oxygenated conditions the SPD occurred reliably in metiamide-treated tissues when the pH of the nutrient solution (pHN) was below 7.1. The SPD was observed also in metiamide-treated tissues exposed to 20 mM luminal or nutrient acetylsalicylic acid (ASA) with pHN = 7.3, an effect that was abolished by increased nutrient HCO3- concentration. The SPD occurred when NO3- but not isethionate or acetate replaced Cl- in the bathing media. A marked increase in potential difference in response to changing luminal Cl- concentration was observed after the SPD, uptake of Cl- from the luminal solution into the tissue increased, but transmural fluxes of Cl- decreased bidirectionally. Permeability to H+ was unaltered in the post-SPD state. An SPD never occurred in antrum under conditions causing SPD in fundus, suggesting that oxyntic cells are prerequisite. We conclude that, under conditions which cause tissue or cellular acidosis and cessation of H+ secretion, fundic mucosae respond with an anion-selective increase in apical permeability manifest as the SPD.