Studies of the binding of tritiated sulfidopeptide leukotrienes (LTs) to a membrane preparation from rat lung tissue revealed a site specific for LTC4 with a dissociation constant of 4.1 X 10(-8)M. Similar experiments with a guinea pig lung preparation demonstrated binding specific for LTD4 with a dissociation constant of 2.1 X 10(-10)M. The divalent cations Ca++, Mg++, and Mn++ significantly enhanced the affinity of binding of the respective LTs to both sites. The binding of LTC4 to guinea pig lung and rat lung exhibited similar characteristics, but the former was observed only in the presence of the gamma-glutamyl transpeptidase inhibitor, serineborate complex. The binding affinities of various isomers of both sulfidopeptide LTs paralleled the potency of their pharmacologic effects, which supports the contention that the sites are receptors specific for LTC4 and LTD4. The slow-reacting substance of anaphylaxis antagonist, FPL 55712, had a higher affinity for the LTD4 receptor, which is consistent with its more effective antagonism of the LTD4-induced contractile response of guinea pig lung parenchymal strips. The ability of Na+ and guanosine triphosphate to inhibit the binding of LTD4 suggests that the action of LTD4 is associated with a depression of intracellular concentrations of cyclic adenosine monophosphate.