Histamine concentrations in the gastric mucosa, gastric vein blood, and gastric contents were measured after instillation of 300 ml of 40%, 20% and 12.5%, vol/vol, ethanol intragastrically for 30 min in anesthetized dogs. The mean histamine concentration in the gastric mucosa, gastric vein blood, and gastric contents in dogs treated with 40% ethanol was significantly higher than in dogs treated with sodium chloride (NaCl). Serial studies of the gastric vein blood of the ethanol-treated dogs should significant elevation of histamine concentrations for 2 hr after instillation of 40% ethanol, but less increases at 20 and 30 min after instillation of 12.5% and 20%, respectively. No change was observed after administration of 50% glucose and 25% mannitol. Morphologically, the gastric mucosa of the ethanol-treated dogs was edematous, congested and hemorrhagic. The severity of these changes increased with the concentration used. The mucosa of the dogs treated with sodium chloride, glucose, or mannitol was normal. The factors that may underlie the increase in histamine concentrations in the gastric vein blood and the possible relation of such an increase to the morphologic alterations are discussed.