Epithelial repair after luminal acid exposure was studied in the rabbit duodenum in vivo and in vitro. Hydrochloric acid (200 mM, 30 min in vivo; 10 mM, 10 min in vitro) caused a uniform damage of the mucosa confined to the villi. After demarcation and detachment of the necrotic tissue the defect was bridged by the remaining viable epithelial cells, resulting in a reduction of villus height. This process of mucosal repair proceeded continuously, so that 9 h after acid damage only 33% of villi in the proximal duodenum and 41% in the distal duodenum remained not fully restored, at both luminal pH 7 and luminal pH 3. The difference is due to the higher acid susceptibility of the distal duodenum. In vitro, most of the mucosal surface was reconstituted 5 h after acid injury, at both luminal pH 7.4 and luminal pH 3. The potential difference declined and reversed after mucosal damage; restitution to original values was only observed at luminal pH 7 in vivo and luminal pH 7.4 in vitro.