The role of duodenogastric reflux in the pathogenesis of gastroesophageal reflux disease is not clear. Using hepatobiliary scanning techniques, we found evidence of duodenogastric reflux in six of 13 patients with Barrett's esophagus. This compares with only two positive studies in 19 control subjects. This difference is statistically significant (P = 0.038, two-tailed Fisher's exact test). Three of nine patients who had gastroesophageal reflux without Barrett's esophagus had evidence of duodenogastric reflux, a frequency not significantly different from either of the other groups. Gastroesophageal reflux of bile and pancreatic enzymes, in addition to gastric acid may contribute to the greater esophageal damage often seen in Barrett's esophagus. The presence of duodenogastric reflux in these patients may have important pathophysiologic and therapeutic implications.