The inhibitory actions of intravenous somatostatin on the gastric secretory responses to pentagastrin (1.5 microng/kg-h i.v.) and to a meal (10% peptone, pH 5.5) were studied in six healthy subjects. Meal-induced gastric acid output was estimated by means of a modified Fordtran and Walsh method of intragastric titration. Somatostatin (5 microng/kg-h; cyclic form) significantly inhibited the total 1-hour acid response to pentagastrin by about 70% (inhibition of pepsin secretion: about 70%) and that to a test meal by about 75%. During the last 30 min of somatostatin infusion the pentagastrin-stimulated secretion of acid was significantly reduced by about 90% (inhibition of pepsin output: about 85%) while the corresponding figure in the test with meal-induced secretion was about 95%. Serum gastric--elevated in response to the test meal--was found to be merely lowered by about 30% during somatostatin infusion. Consequently, it is tempting to assume that inhibition of human gastric acid secretion by exogenous somatostatin largely results from a direct antisecretory effect upon parietal cells and, only to a minor extent, from an indirect action via reduction of gastrin release.