1. The aim of the present experiments was to study the possible involvement of known bronchoconstrictor substances in mediating the myotropic action of endothelin-1 (ET-1, human-porcine endothelin) in guinea-pig isolated airways. 2. ET-1 (1-100 nM) caused a dose-dependent contraction of guinea-pig trachea, upper bronchus and parenchyma. The contractions developed slowly, reaching maximal values 4-6 min after addition of the peptide. 3. The contractile action of ET-1 was significantly attenuated by indomethacin (10 microM), a cyclo-oxygenase blocker. BM 13505 (5 microM), a thromboxane receptor antagonist, FPL 55712 (19 microM) and YM 16638 (1 microM), antagonists of the sulphidopeptide leukotrienes, BN 52021 (10 microM) and WEB 2086 (1 microM), platelet-activating factor receptor antagonists in all three tissue preparations studied. 4. Pretreatment of the airway tissues with compound U 75302 (3 microM), a selective leukotriene B4 receptor antagonist, or with a mixture of antagonists containing methysergide (0.75 microM), phentolamine (0.4 microM), propranolol (13 microM), atropine (0.4 microM) and diphenhydramine (0.45 microM) did not modify the myotropic action of ET-1. 5. ET-1, 10 and 100 nM induced three, and nine fold increases in thromboxane A2 release from lung parenchymal strips. 6. ET-1-induced thromboxane A2 release was completely abolished by indomethacin, and was significantly attenuated by BN 52021, WEB 2086 and FPL 55712. Neither BM 13505 nor YM 16638 exerted a significant effect on thromboxane release. 7. The present findings show that contraction of guinea-pig airway smooth muscle by ET-1 is mediated, in part, by the release of thromboxane A2, sulphidopeptide leukotrienes and platelet-activating factor, and suggest that the increased thromboxane A2 release following ET-1 is partly a consequence of enhanced synthesis of sulphidopeptide leukotrienes and platelet-activating factor.