Deoxycholate-induced colonic injury and repair were studied both functionally and morphologically utilizing in vivo loop preparations of the porcine colon. The mucosa was exposed to (a) varying doses (1.5 to 21 mM) of deoxycholate for 30 minutes, (b) 15 mM deoxycholate for varying times and (c) 15 mM deoxycholate for 30 minutes with varying times of recovery. Colonic permeability was assessed by mannitol clearance from blood to lumen and transmural potential difference. After colonic perfusion, tissue samples were collected for light and electron microscopy. Both the degree of mucosal permeability and the amount of superficial epithelial damage increased with increasing concentrations of bile salt culminating in cell necrosis and epithelial sloughing. Denuded colonic surfaces became reepithelialized by migrating, flattened cells in as little as 15 minutes of recovery. Relatively normal appearing columnar epithelium was restituted within 2 hours. Mannitol clearance returned to control values after 30 minutes of recovery, whereas it took potential difference 2 hours of recovery to return to normal. The results of these experiments suggest that (a) the permeability changes measured are most likely due to the lytic action of bile salts which leads to cell degeneration and sloughing of the superficial epithelium, (b) epithelial restitution after superficial damage is remarkably rapid, (c) the formation of a flattened epithelium of immature cells is adequate for restoration of the barrier to macromolecules but ion transport or resistance is slower to recover and (d) repair is due to an active ameboid movement of viable cells out of the crypts onto the surface of the colon.