1 The effect of a specific histamine H2-receptor antagonist, metiamide, on the acid dose-response curves for pentagastrin or methacholine was studied in rats provided with Heidenhain pouches. 2 Metiamide induced a shift to the right of the dose-response curve to pentagastrin and lowered the maximal secretion.3 In contrast, metiamide only increased the ED50 for methacholine but did not alter the calculated maximal response. 4 The effect of metiamide on pentagastrin and methacholine-induced secretion is in agreement with the previously suggested difference in the part played by mucosal histamine in the mode of action of the two stimulatory agents.