The effects of a highly selective leukotriene D₄ receptor antagonist, ICI 204.219, on allergen-induced bronchoconstriction and changes in airway reactivity were evaluated in a double-blind, placebo-controlled, crossover trial. Ten atopic subjects were selected for the study on the basis of an immediate fall in forced expiratory volume in 1 s (FEV₁) of at least 15% and a least a doubling dose fall in their PC₂₀-histamine (the concentration of histamine needed to reduce FEV₁ by 20%) after antigen challenge. Baseline PC₂₀-histamine was determined before the ingestion of a single oral 40 mg dose of ICI 204.219 or matched placebo. 2 h later subjects were challenged with aerosolised allergen; FEV₁ was measured for the next 6 h then PC₂₀-histamine was remeasured. Two subjects did not complete the study for reasons not related to the trial medication. ICI 204.219 significantly attentuated the early and late phase bronchoconstriction to inhaled allergen (mean treatment difference in area under the FEV₁-time curves 2529 [95% Cl 1085-3972] Δ%FEV₁.min; p<0·005: and 3537 [528-6545] Δ%FEV₁.min; p < 0·03) and suppressed the allergen-induced increase in non-specific bronchial reactivity (mean treatment difference 1·03 [0·34-1·71] doubling dilutions of histamine; p<0·01). These findings suggest that ICI 204.219 may be a disease-modifying agent in asthma. Further studies are under way to evaluate its clinical efficacy.