Influence of luminal Ca2+ on the integrity of normal mucosa and recovery of damaged mucosa in anesthetized rat stomachs was studied using a perfusion system. Changes in the mucosal integrity were monitored by measuring transmucosal potential difference (PD) and luminal pH. EDTA, a Ca2+ chelator, dose-dependently reduced PD and increased luminal pH. Five mM Ca2+ (CaCl2) alone produced no changes in either PD and luminal pH, but the PD which was reduced by 250 mM EDTA was significantly recovered. Ethanol or NaCl concentration-dependently reduced PD, but gradually reverted to baseline levels. While 5 mM Ca2+ or 5 mM EDTA did not influence the reduction in PD with 50% ethanol and 1 M NaCl, these agents either enhanced or delayed the recovery processes in reduced PD, respectively. Five mM Ca2+ enhanced the recovery of PD which was reduced by 50% ethanol plus 5 mM EDTA. Gastric damage induced by 50% ethanol plus 5 mM EDTA was much more severe than that induced by 50% ethanol alone or 50% ethanol plus 5 mM Ca2+. Both 50% ethanol and 1 M NaCl significantly increased Ca2+ contents in the gastric lumen. Luminal Ca2+ appears to play an important role in maintaining mucosal integrity, under normal physiological conditions, and in accelerating the recovery process of damaged mucosa in rat stomachs.