The interaction between the triazolothienodiazepine WEB 2086 and the in vitro and in vivo bronchopulmonary effects of PAF-acether and active/passive anaphylaxis in the guinea-pig was studied. WEB 2086 (1–100 nM) inhibited PAF-acether (10–100 ng)-induced bronchoconstriction and TXB 2 release from isolated and perfused guinea-pig lungs without affecting the response to 100 μg arachidonic acid. In addition, 1–10 μM WEB 2086 significantly reduced antigen-induced TXB 2 and histamine release from lungs from actively and passively sensitized guinea-pigs. In the presence of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), mepyramine, methysergide, indomethacin and atropine, WEB 2086 (20–50 μM) inhibited by 30–40% the residual contraction of lung parenchyma strips from guinea-pigs actively sensitized by 0.1–10 μg antigen. In vivo, WEB 2086 (0.1–1 mg/kg) reversed or abolished the bronchoconstriction, hypotension, thrombocytopenia and leukopenia evoked by perfusion of PAF-acether (3 or 44 ng/kg per min). At 3 mg/kg, WEB 2086 also markedly decreased the bronchoconstriction and leukopenia induced by 100 μg/kg antigen in mepyramine (5 μg/kg)-treated passively sensitized guinea-pigs. In contrast, WEB 2086 was ineffective against active anaphylaxis in vivo. These results demonstrate that WEB 2086 antagonizes the bronchopulmonary effects due to PAF-acether and to anaphylactic shock in the guinea-pig.