To determine whether the action of leukotriene E4 is mediated by its cross reaction with leukotriene D4 receptor sites, we compared [3H] leukotriene E4 and [3H]leukotriene D4 binding activities in selected tissues as well as their competition results in the guinea-pig crude lung membrane. We demonstrated good correlation of [3H]leukotriene E4 and [3H]leukotriene D4 binding activities among the tissues studied. A significant correlation was demonstrated between the ability of leukotriene C4, D4 and E4, FPL-55712 and arachidonic acid to inhibit lung [3H]leukotriene E4 and [3H]leukotriene D4 binding. These correlations suggest that leukotriene E4 binds to a site which is similar to or close to the leukotriene D4 receptor.