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Barrett's oesophagus is an important clinical problem that can lead to oesophageal adenocarcinoma. A variety of mucosal ablation strategies are now being applied in an attempt to prevent this, although they all can cause complications. Animal experiments that suggest that ethylenediaminetetraacetic acid (EDTA) could be a novel agent for ablation of Barrett's oesophagus are reported in this article.Dark Agouti rats were used in all experiments. To determine the feasibility of using EDTA to strip intestinal type mucosa, segments of the small intestine were exposed in vitro to EDTA at various concentrations with or without agitation. The conditions required for EDTA to strip mucosa from a vascularized loop of small bowel were then optimized in vivo. Cannulated small bowel loops were irrigated with different concentrations of EDTA with or without pulsation of the irrigation solution. The effect of similar treatments on the normal mucosa of the rat oesophagus was then determined. Mucosal healing after EDTA stripping was studied in an isolated small bowel loop survival model.Ethylenediaminetetraacetic acid with agitation or pulsation resulted in stripping of the intestinal columnar mucosa in vitro and in vivo. The extent was influenced by the concentration of EDTA and duration of exposure. Squamous epithelium was relatively resistant to stripping. In the survival model the small bowel mucosa regenerated without stricture formation.Small bowel columnar mucosa can be removed by EDTA in vivo without stricture formation. A refinement of this approach could be applicable to the ablation of Barrett's oesophagus.