The cysteinyl leukotrienes-leukotriene C-4(LTC4), leukotriene D-4(LTD4) and leukotriene E-4(LTE4)-are important mediators of human bronchial asthma(1-3). Pharmacological studies have determined that cysteinyl leukotrienes activate at least two receptors, designated CysLT(1) and CysLT(2) (refs 4-6). The CysLT(1)-selective antagonists, such as montelukast (Singulair)(7-10), zafirlukast (Accolate)(11) and pranlukast (Onon)(12), are important in the treatment of asthma. Previous biochemical characterization of CysLT(1) antagonists and the CysLT(1) receptor has been in membrane preparations from tissues enriched for this receptor(13). Here we report the molecular and pharmacological characterization of the cloned human CysLT(1) receptor. We describe the functional activation (calcium mobilization) of this receptor by LTD4 and LTC4, and competition for radiolabelled LTD4 binding to this receptor by the cysteinyl leukotrienes and three structurally distinct classes of CysLT(1)-receptor antagonists. We detected CysLT(1)-receptor messenger RNA in spleen, peripheral blood leukocytes and lung. In normal human lung, expression of the CysLT(1)-receptor mRNA was confined to smooth muscle cells and tissue macrophages. Finally, we mapped the human CysLT(1)-receptor gene to the X chromosome.