The effects of gastric acid antisecretory agents prostaglandins E2, I2 (PGE2, PGI2) and somatostatin on pentagastrin-stimulated gastric histamine and N tau-methyl histamine secretory rates were examined in anesthetized mixed breed dogs. We infused two gastric acid antisecretory doses of PGE2 and PGI2 to test the effect of prostaglandins on pentagastrin-stimulated gastric histamine release. Neither dose of PGE2 and PGI2 had an effect on pentagastrin-stimulated histamine and N tau-methyl histamine release, even though the prostaglandins caused marked gastric vasodilation. In addition, the infusion of the higher dose of PGE2 and PGI2 alone had no effect on histamine secretory rates. In contrast, somatostatin inhibited both pentagastrin-stimulated gastric histamine release by approximately 95% as well as basal histamine release by approximately 60%. Somatostatin also inhibited the pentagastrin-stimulated N tau-methyl histamine secretory rates. The results indicate that neither PGE2 nor PGI2 at antisecretory doses affect pentagastrin-stimulated gastric histamine release, but somatostatin has a very potent inhibitory effect in that regard. Our data suggest that the mechanisms by which prostaglandins and somatostatin affect gastric acid secretion may be diverse.