The cysteinyl leukotrienes (cysLTs), LTC4, LTD4, and LTE4, mediate their actions through two distinct G protein-coupled receptors. LTD4 is the preferred ligand for the cysLT1 receptor, whereas LTC4 and LTD4 bind with approximately equal affinity to the cysLT2 receptor. MK-571 is a selective, orally active CysLT1 receptor antagonist. It blocks the binding of LTD4, but not LTC4, to human and guinea pig lung membranes with Ki values of 0.22 nM and 2.1 nM, respectively, which is indicative of CysLT1 receptor-mediated activity in these preparations. MK-571 effectively blocks LTD4 activation of recombinant human and mouse CysLT1 receptors but is ineffective at blocking LTC4 or LTD4 activation of the recombinant human or murine CysLT2 receptors. MK-571 is also a potent inhibitor of the multidrug resistant protein 1 (MRP1).