In laboratory rodents, concentrations of reduced glutathione (GSH) are exceedingly high (up to 7 to 8 millimolar) in the glandular gastric tissue compared to concentrations in other portions of the gastrointestinal tract or to those of most other organs. Gastric GSH varies diurnally, with the highest levels occurring in the late afternoon or early evening. Starvation, treatment with diethyl maleate, or cold-restraint stress all caused marked decreases in stomach GSH, whereas treatment with cobaltous chloride caused an increase in the GSH concentrations. The physiological significance of the high gastric GSH is unknown, but because this endogenous compound may strongly modulate (decrease or increase) the macromolecular binding of certain chemicals capable of inducing stomach tumors, the possible role of glutathione in the pathogenesis of chemically induced gastric cancer should be considered.