Arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. To examine the development of lipoxygenase metabolites of arachidonic acid in cerebral ischemia, we measured the concentration of leukotriene C4 in the gerbil forebrain following ischemia, and pretreated several animals with cyclooxygenase and lipoxygenase inhibitors. The leukotriene C4 concentration was significantly increased 1 hour after transient ischemia and cerebral edema. The incerase in the concentration of leukotriene metabolites was significantly suppressed by preteratment with the lipoxygenase inhibitors except for the cyclooxygenase inhibitor and phospholipase A2 inhibitor. Intracerebral cerebral injection of leukotriene C4 produced local intracerebral edema. Cycloxygenase inhibition may result in increased substrate availability for the lipoxygenase system. Studies of such an interaction help elucidate the pharmacological modification of detrimental vascular changes after transient cerebral ischemia.