Somatostation has been postulated to have a paracrine modulating role in gastrin and gastric acid secretion. We applied the organ culture technique to examine somatostatin release by explants of human gastric mucosa taken from patients with active duodenal ulcer, from control subjects, and from patients with pernicious anemia. Somatostatin was found to be released at a constant rate by antral explants during 3 h of incubation. In active duodenal ulcer antral and fundic 2-h somatostatin release (18.7 +/- 2.6 pg/mg tissue (means + SE), n = 75; and 27 +/- 3 pg/mg tissue, n = 94, respectively) was significantly lower than release by control antral and fundic mucosa (83 +/- 17 pg/mg tissue, n = 39, and 72 +/- 16 pg/mg tissue, n = 42, respectively) (P less than 0.01). Somatostatin release by antral and fundic mucosa of patients with pernicious anemia was also significantly decreased (20 +/- 8 pg/mg tissue, n = 12, and 7.6 +/- 2 pg/mg tissue, n = 12, respectively) (P less than 0.05). These results imply possible impairments of the paracrine release of somatostatin in peptic ulcer disease and in pernicious anemia.