In order to explore secretory mechanisms in peptic ulcer, the plasma secretin response to an intraduodenal load of gastric acid stimulated with tetragastrin was studied in 10 patients with duodenal ulcer, nine with gastric ulcer, and five young healthy volunteers. After the injection of tetragastrin plasma secretin level was significantly increased in all subjects. The integrated incremental secretin output significantly correlated with the incremental acid output in the duodenal ulcer group as well as the gastric ulcer group. THere was no significant difference in the integrated incremental secretin output among the three groups. However, the integrated incremental secretin output per unit amount of gastric acid loaded in the duodenum was significantly lower in the duodenal ulcer group than in the other two groups. These results suggest that in patients with duodenal ulcer the secretin release in response to an intraduodenal load of endogenous acid is impaired.