The role of histamine-1 receptors in modulating gastric acid secretion was evaluated in anesthetized dogs with gastric fistulas. Histamine receptor agonists were infused directly into the gastric artery supplying the fundus to avoid any systemic hemodynamic effects. Two experimental approaches were taken to try to determine whether histamine-1 receptors participate in the control of acid secretion. Firstly, we measured the effect of the H1-receptor antagonist, hydroxyzine dihydrochloride, on histamine and dimaprit stimulated acid secretion. Secondly, we measured the effect of H1-receptor agonist on dimaprit stimulated gastric secretion. Although H1-receptor antagonist enhanced stimulated gastric acid secretion to histamine, the antagonist also enhanced stimulated gastric acid secretion to dimaprit (H2-agonist), suggesting that the enhanced gastric acid secretion after administration of H1-receptor antagonist is not because of the inhibition of histamine receptor at the gastric fundus. In addition, 2 doses of H1-receptor agonist infused into the gastric fundus had no effect on dimaprit stimulated gastric acid secretion. These data suggest that H1-receptors do not modulate gastric acid secretion at the level of the gastric fundus in the dog.