We examined the ability of the inhaled leukotriene D4 antagonist (L-648,051) to inhibit antigen-induced asthmatic responses. Twelve patients with stable exogenous asthma participated in two separate double-blind, placebo-controlled, cross-over trials. The ability of the antagonist to reverse or inhibit antigen-induced bronchoconstrictor response was examined; both the immediate and the late phases were studied. In the reversal study, patients inhaled 800 micrograms of L-648,051 during the immediate phase (15 min after antigen challenge) and again during in the late phase (7 h after antigen challenge). In the prevention study, the same dose (800 micrograms) of L-648,051 was inhaled before the expected immediate reaction (5 min before antigen challenge) as well as before the expected late reaction (2.5 h after antigen challenge). The LTD4 antagonist was not effective in reversing the airway response to inhaled antigen, as measured by airway resistance (Rt), forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC). When the antagonist was given prior to antigen challenge, a slight reduction in Rt was observed during the immediate phase, but not during the late phase. Some improvement in FEV1 and FVC during the immediate phase was also observed, but these changes did not reach statistical significance. These results suggest that LTD4 plays a role in the immediate phase of antigen-induced asthma.