Zafirlukast is an orally active and selective cysteinyl leukotriene (cysLT) receptor antagonist. In humans, zafirlukast antagonized the effects of exogenously administered LTD4 and cysLTs released endogenously in response to physical and chemical stimuli. Zafirlukast antagonized LTD4-induced bronchoconstriction, with effects still evident 12 h after drug administration. In clinical models of asthma, zafirlukast inhibited bronchospasm after allergen or exercise challenge in patients with asthma. In multicenter trials in patients with chronic, stable asthma, zafirlukast reduced asthma symptoms, decreased as-needed beta-agonist use, and improved pulmonary function without increasing the number of adverse events. Zafirlukast also exhibited evidence of an anti-inflammatory effect in the lung in preliminary studies involving segmental antigen challenge. The results from these clinical trials demonstrate that zafirlukast is effective and safe for the prophylactic treatment of asthma.