The effect of histamine and secretin infusions on gastric secretory volume and acid production has been studied in 22 patients with peptic ulcer disease and one normal volunteer. Some of these patients had normal mucosa; some had gastric mucosal hypertrophy and/or antritis. During histamine infusion the mean pH was 1.14 and the mean secretory volume was 351 cc/hr. With histamine-secretin infusion these values rose to 3.51 and 584 cc/hr, respectively. Duodenal regurgitation was excluded by appropriate studies in seven studies. Patients infused with histamine alone for four hours showed no change in pH or secretory volume. Five patients had secretin infusion only. During the basal period their mean pH was 4.24 and mean secretory volume 101.2 cc/hr. During the period of secretin infusion these values rose to 8.14 and 278.6 cc/hr, respectively. Statistical analysis of these findings suggests that the production of an alkaline fluid during the secretin infusion is related to antritis. These findings differ from previous studies in which secretin was given either alone or in combination with histamine infusion. The clinical or pathological significance of these observations is discussed.