Anti-IgE at a fixed dilution (1:1000) contracted human airways that had been pretreated with atropine (1 microM), indomethacin (3 microM) and chlorpheniramine (1 microM). This response was blocked by the potent leukotriene synthesis inhibitor BAY x 1005 ((R)-2-[4-(Quinolin-2-yl-methoxy)phenyl)-2-cyclopentyl acetic acid]. The leukotriene synthesis inhibitor MK-886 also blocked the contraction, but BAY x1005 was approximately 10-fold more potent than MK-886 (the IC50 values were 0.27 microM and 3.4 microM for BAY x1005 and MK-886, respectively). BAY x1005 (1 microM) did not alter LTD4 cumulative concentration-effect curves on human airways. Bronchial muscles derived from different levels of the respiratory tract released small quantities of LTE4 (proximal, 7.99 +/- 1.25 ng/g tissue wet wt.; distal, 13.12 +/- 4.46 ng/g tissue wet wt.). These basal levels were significantly increased when the preparations were challenged with a fixed dilution (1:1000) of anti-IgE (proximal, 21.84 +/- 5.33 ng/g tissue wet wt.; distal 72.13 +/- 30.70 ng/g tissue wet wt.). Indomethacin (3 microM) did not alter either the basal amounts or the levels of LTE4 measured during anti-IgE stimulation. However, BAY x1005 or MK-886 in the presence of indomethacin prevented the increase in LTE4 levels that were observed during anti-IgE challenge. In these protocols the IC50 values obtained were 0.18 microM and 1.42 microM for BAY x1005 and MK-886, respectively. These data demonstrate that BAY x1005 is a potent leukotriene synthesis inhibitor in human airways.