1. We have studied the peptic responses of the intact human stomach to stimulation by doses of pentagastrin which elicit a maximal acid response.2. In twelve patients an intramuscular injection of pentagastrin (6 mug/kg) was followed by a prompt increase in acid output which attained a peak value eight times higher than the basal value in the period 15-30 min after stimulation. The pattern of the peptic response was similar, but the peak output of pepsin was only three times the output in unstimulated juice.3. In ten subjects the acid and peptic responses to I.V. infusion of pentagastrin (1.2 mug/kg per hr) were studied using a gastric perfusion technique with (14)C-labelled polyethylene glycol as non-absorbable marker. In seven of these ten subjects the pH of duodenal contents exceeded 6, and less than 0.5 m-mole HCl per 15 min entered the duodenum throughout the tests. In this subgroup pentagastrin evoked a strong acid response but no peptic response.4. In three subjects the pH of duodenal juice was less than 5.5 at times when more than 1 m-mole HCl per 15 min entered the duodenum. The acid response to pentagastrin differed considerably in the three subjects, but in each individual the output of pepsin increased each time an excess of HCl entered the duodenum.5. Since pentagastrin infused in a dose which maximally stimulates acid did not significantly increase the output of pepsin provided no HCl entered the duodenum we conclude that pentagastrin does not stimulate the secretion of pepsin in man. The transient insignificant peptic response to pentagastrin infusions, and the small but significant response to bolus injections of pentagastrin, can be explained as a wash-out phenomenon.