The influence of misoprostol pretreatment (100 micrograms/loop intraluminally) on small intestinal damage induced by acetic acid was evaluated in anesthetized rabbits. In this model injury was induced by intraluminal administration into loops of distal small intestine, of a solution of calcium gluconate (50 mg/ml) and acetic (200 mM). After 3 hr damage was associated with increase in loop fluid volume, loop fluid protein levels and epithelial permeability to 51Cr-EDTA, all of which were attenuated by misoprostol pretreatment. Similar protective effects were noted 45 min after the insult, suggesting that misoprostol may be therapeutically useful in conditions where the epithelial barrier is compromised.