Background & Aims: In Helicobacter pylori-induced gastritis, oxidants are generated through the interactions of bacteria, activated granulocytes and cells of the gastric mucosa. In this study we explored the ability of one class of oxidants, represented by monochloramine (NH₂Cl), to serve as agonists of Ca²⁺ accumulation within the parietal cell of the gastric gland. Methods: Isolated rabbit gastric glands were loaded with the fluorescent reporters for Ca²⁺ in the cytoplasm (fura-2AM) or intracellular stores (mag-fura-2AM). Conditions were adjusted to screen contributions from metal cations such as Zn²⁺, for which these reporters have affinity. Results: Exposure to NH₂Cl (up to 200µM) led to dose-dependent increases in intracellular Ca²⁺ ([Ca²⁺]_i), in the range of 200 to 400nM above baseline. Further studies indicated that NH₂Cl-induced accumulation of Ca²⁺ in the cytoplasm is due to release from intracellular stores, entry from the extracellular fluid, and impaired extrusion. These alterations were prevented by the oxidant scavenger vitamin C or a thiol-reducing agent, dithiothreitol (DTT). Introduction of Vitamin C during ongoing exposure to NH₂Cl arrested but did not reverse accumulation of Ca²⁺ in the cytoplasm. In contrast, introduction of DTT or N-acetylcysteine (N-Ac) arrested and partially reversed the effects of NH₂Cl. Conclusions: Ca²⁺-handling proteins are susceptible to oxidation by chloramines, leading to sustained increases in [Ca²⁺]_i. Therefore, under certain conditions, NH₂Cl may act not as an irritant but as an agent that activates intracellular signaling pathways. In addition, anti-NH₂Cl strategies should take into account different effects of oxidant scavengers and thiol-reducing agents.