Previous studies in asthmatics have demonstrated that the endogenous release of inhibitory prostaglandins limits the bronchoconstrictor response to repeated challenges with exercise and histamine, and that inhaled prostaglandin (PG) E2attenuates allergen-induced asthmatic responses and exercise bronchoconstriction in asthmatics. Inhaled PGE2does not significantly attenuate methacholine airway responsiveness. These results, taken together, indicate that inhaled PGE2attenuates the bronchoconstriction caused by stimuli, such as allergen and exercise, that result in bronchoconstriction through cysteinyl leukotriene (LT) release. The purpose of this study was to determine whether inhaled PGE2could selectively attenuate LTD4-induced bronchoconstriction in seven stable asthmatic subjects. Each subject was studied on four different study days. On two occasions the subjects inhaled 100 mg PGE2, 30 mins before a methacholine, or LTD4challenge test. On the other two study days, the subjects were pretreated with its diluent. Results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PC20). PGE2pretreatment significantly increased the LTD4PC20, but not the methacholine PC20. The mean LTD4PC20increased from 2.00 mg/mL (%SEM 1.65) after diluent pretreatment to 3.01 mg/mL (%SEM 1.64) after PGE2pretreatment (P=0.008). The mean methacholine PC20was 1.28 mg/mL (%SEM 1.68) after diluent pretreatment and 1.62 mg/mL (%SEM 1.46) after PGE2pretreatment (P=0.28). These results suggest that PGE2partially attenuates LTD4-induced bronchoconstriction; however, the magnitude of the effect is unlikely to account for its attenuation of exercise and allergen-induced bronchoconstriction.