The effect of a variety of pharmacological inhibitors and antagonists on the bronchoconstrictor response of the perfused lung to cotton dust (CDE) and bract (BE) extracts was examined. Bronchoconstriction was significantly attenuated by the leukotriene (LT) antagonists FPL55712 and L660,711. Collection of lung perfusate after bronchoconstrictor doses of CDE and BE showed that peptido-LTs and PGF2, were released. On the basis of this pharmacological and biochemical evidence, it is concluded that the bronchoconstriction induced by these two extracts is mediated by release of LT and possibly prostanoids. CDE and BE were also able to release LTs from alveolar macrophages but the significance of this remains to be determined. Bacterial lipopolysaccharide (LPS) in concentrations equal to the LPS content of the doses of CDE had no bronchoconstrictor action on the perfused lung. However, these concentrations of LPS were able to release relatively small amounts of LTs from the perfused lung and alveolar macrophages.