To examine the role of leukotriene D4 (LTD4) in early and late pulmonary responses to antigen, we evaluated the effects of two LTD4, antagonists, MK-571 and FPL-57231, on the changes in pulmonary resistance (RL) in the 8-h period following antigen challenge of allergic rats. A total of 69 rats, aged 6 to 8 wk, were sensitized to subcutaneous ovalbumin (OA, 1 mg) and intraperitoneal Bordetella pertussis vaccine (6 x 10(9) bacilli). At 14 days after sensitization, rats were anesthetized with intraperitoneal urethane (1.1 g/kg) and intubated endotracheally. Aerosols of OA (5% wt/vol in saline for 5 min) were administered to 24 control rats, to 11 rats that were pretreated with aerosolized FPL-57231, and to 8 rats that were pretreated with MK-571; 6 rats also received MK-571 at 2 h after OA. A control group of 13 rats was challenged with aerosols of saline. We defined an early response (ER) as an increase in RL to at least 150% of the postsaline value occurring within 1 h after OA challenge. A late response (LR) was defined as a value of RL exceeding the mean plus 2 SD of all values of RL from 75 min to 8 h after OA challenge and lasting at least 30 min. An ER was observed in 17 of 24 control rats, in 8 of 11 FPL-57231-pretreated rats, and in 3 of 8 MK-571-pretreated rats (not significant). The magnitude and duration of the ER were significantly reduced by MK-571, whereas only the duration was affected by FPL-57231.(ABSTRACT TRUNCATED AT 250 WORDS)