Four dogs were prepared with antrectomies, gastric fistulas, and Pavlov pouches. Insulin or 2-deoxyglucose given by rapid intravenous injection evoked little secretion from the Pavlov pouches. Therefore, a threshold dose of histamine was given by continuous intravenous infusion and insulin, 0.5 or 0.25 U per kg, or 2-deoxyglucose, 0.15 g per kg, was injected after acid secretion had reached a plateau. This resulted in secretory responses similar to those stimulated by insulin or 2-deoxyglucose in animals with intact antrums. In some experiments secretin, 2 U per kg-hr was added to the intravenous infusion at the time of insulin or 2-deoxyglucose injection. Secretin did not alter acid output in response to insulin or 2-deoxyglucose. Pepsin secretion after 2-deoxyglucose was enhanced by secretin but secretin did not change an already high pepsin response to insulin. Acid and pepsin secretion stimulated by a continuous intravenous infusion of bethanechol was compared with secretory rates when secretin was added to the infusion. Secretin depressed acid and increased pepsin output due to bethanechol. These results were contrasted with those from experiments performed in dogs with gastric fistulas, Pavlov pouches, and intact antrums. In these animals, secretin markedly inhibited acid secretion in response to insulin or 2-deoxyglucose. These data suggest that direct cholinergic stimulation of parietal cells is not vulnerable to inhibition by secretin. The inhibition observed in animals with intact antrums is probably due to an antagonism by secretin of vagally released gastrin. Since bethanechol-stimulated acid secretion was inhibited by secretin in antrectomized animals the response to bethanechol may be due to the release of an endogenous humoral gastric stimulant other than antral gastrin as well as a direct effect of bethanechol on parietal cells.