The cysteinyl leukotrienes—leukotriene C₄(LTC₄), leukotriene D₄(LTD₄) and leukotriene E₄(LTE₄)—are important mediators of human bronchial asthma^,,,. Pharmacological studies have determined that cysteinyl leukotrienes activate at least two receptors, designated CysLT₁ and CysLT₂ (,,). The CysLT₁-selective antagonists, such as montelukast (Singulair)^,,,, zafirlukast (Accolate) and pranlukast (Onon), are important in the treatment of asthma. Previous biochemical characterization of CysLT₁ antagonists and the CysLT₁ receptor has been in membrane preparations from tissues enriched for this receptor. Here we report the molecular and pharmacological characterization of the cloned human CysLT₁ 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 CysLT₁-receptor antagonists. We detected CysLT₁-receptor messenger RNA in spleen, peripheral blood leukocytes and lung. In normal human lung, expression of the CysLT₁-receptor mRNA was confined to smooth muscle cells and tissue macrophages. Finally, we mapped the human CysLT₁-receptor gene to the X chromosome.