The aim of this study was to explore the feasibility of an endoscopic approach to gastric vagotomy using the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser in dogs. Based on gross and histologic measurements, target zones for endoscopic vagotomy were defined with reference to mucosal side landmarks. Target zones containing the unbranched segments of the major intramural vagal branches were linear and symmetrically located anterior and posterior to the midline of the lesser curvature extending from the level of the esophagogastric junction to the proximal antral border. Because of minimal variability between dogs, this zone could be accessed endoscopically and reliably injured. Unfortunately, it was necessary to produce a nearly full thickness burn to interrupt the deep intramural vagal branches. Despite efforts to control dosimetry, delayed perforations occurred in three of four dogs. We conclude that endoscopic gastric vagotomy using the Nd:YAG laser is not feasible in the dog model because of difficulty controlling the depth of thermal injury. An endoscopic approach to vagotomy remains conceptually appealing because of the predictable location of and accessibility to a target zone.