The air spaces of isolated lung of the guinea pig were perfused at a constant rate with Krebs saline. Bronchoconstriction induced by introduction of extracts of cotton dust (CDE) and bract (BE) was measured as a rise in perfusion pressure. The responses to both bronchoconstrictor agents were not significantly different when elicited in either non-lavaged or lavaged lungs. This suggests that alveolar macrophages may not be a major site of action for CDE and BE for the induction of bronchoconstriction in this preparation. The effect of several pharmacological agents having an influence at various loci in the arachidonic acid cascade was examined. Partial blockade of CDE- and BE-induced bronchoconstriction occurred in the presence of dexamethasone, indomethacin and the leukotriene antagonists FPL55712 and L-660,711. WY48252, which is a luekotriene DA receptor antagonist as well as an inhibitor of 5-lipoxygenase and cyclooxygenase, exerted a profound inhibitory effect on the bronchoconstrictor action of the extracts. The PAF antagonist, WEB2086, also attenuated the response of the lung to CDE and BE. The results support the hypothesis that the acute effects of these extracts on the airways of this lung preparation are due largely to the formation of bronchoactive metabolites of membrane phospholipids. On this preparation, a high concentration of vitamin C exerted a selective inhibitory action on the BE-induced bronchoconstriction.