This study was designed to determine the influence of leukotriene C4 on gastric acid and alkaline secretion. Leukotriene C4 was found to be a potent inhibitor of gastric acid secretion induced in vagally innervated and denervated portions of the stomach of conscious dogs by a variety of stimulants such as histamine, pentagastrin, and meat feeding. Leukotriene C4 was also an effective inhibitor of acid formation in the isolated gastric glands stimulated by histamine or dibutyryl cyclic adenosine monophosphate without or with addition of indomethacin, indicating that this compound acts directly on the parietal cells without mediation of endogenous prostaglandins. Leukotriene C4 was also an effective stimulant of gastric alkaline secretion. However, this effect was probably mediated by an increase in the generation of endogenous prostaglandin, as it was accompanied by an increase in the luminal release of prostaglandin E2 and indomethacin prevented both the stimulation of alkaline secretion and luminal prostaglandin E2 release by leukotriene C4.