The aim of this study was to localize the region of the stomach responsible for triggering distension-induced transient lower esophageal sphincter relaxation (TLESR). The canine stomach was partitioned into subsegments by a row of buttressed sutures. This separated either the fundus from the lesser curve or the proximal stomach from the antrum. After 1 mo each region was progressively distended while gastroesophageal pressures were monitored. At the time of the first TLESR, gastric wall tension was estimated from the bag pressure and volume. Distension of the intact stomach, lesser curve, or proximal stomach in 12 dogs produced a progressive increase in lower esophageal sphincter (LES) pressure, which was interrupted at low gastric wall tension (29, 35, and 40 mmHg.cm, respectively) by a superimposed TLESR. Background LES pressure fell progressively with distension of the antrum but was unchanged by distension of the fundus alone. Both the fundus and antrum had significantly higher thresholds for triggering TLESR (96 and 105 mmHg.cm). In another two dogs truncal vagotomy performed at the time of gastric partitioning prevented both the change in background LES pressure, and the triggering of TLESR, associated with proximal gastric and antral distension. We conclude that the subcardiac region of the stomach is primarily responsible for triggering TLESR induced by distension and that the effect on background LES pressure depends on the region distended.