In patients with asthma, increased sensitivity of airway sensory nerves may be involved in producing bronchospasm and cough. To evaluate the effect of a leukotriene-modifying agent on cough reflex sensitivity, we measured the cough response to inhaled capsaicin before and after a 1 4-day course of therapy with zafirlukast, a cysteinyl leukotriene receptor antagonist, in a group of stable asthmatics. The concentration of capsaicin inducing two or more (C2) and five or more (C5) coughs was not altered by zafirlukast, even in those subjects demonstrating a significant change (increment or decrement) in forced expiratory volume in 1 sec (FEV1). These findings support previous evidence that cough and bronchoconstriction are modulated by distinct neural pathways.