The ability of IgE anti-arsenilate hapten-sensitized bone marrow-derived mast cell line (IBD-8) to generate leukotriene C, (LTC,) and increase vascular permeability, and neutrophil infiltration in vivo in Balbk mice challenged with arsenilated BSA (ARS-BSA) was studied. Sensitized 1BD8 cells (5-10 x 10') were administered intraperitoneally followed by 0.1 I*.g ARS-BSA. Following CO, asphyxia, the peritoneal contents were harvested and assayed for immunoreactive LTC, (iLTC,) by radioimmunoassay. Maximal production of iLTC, (60 ng/mouse) was seen 2.5 min after challenge and then decreased to a nadir at 15 min. Animals which were depleted of resident peritoneal cells by treatment with cyclophosphamide gave an iLTC, response equivalent to non-treated controls, indicating that the transferred cells contributed most of the iLTC, response. The oral administration of the 5-lipoxygenase (5-LO) inhibitors, phenidone, SK&F 107649, and the pyridinyl imidazoles SK&F 104493 and SK&F 105809 all reduced the iLTC, response (61-96% inhibition); whereas the vasoactive amine antagonist cyproheptadine and the cyclooxygenase inhibitors, meclofenamic acid and naproxen, had no effect. Extravasation of Evans blue dye was also monitored spectrophotometrically and was significant 5 min after challenge and reached a plateau at 45 min. Like i LTC,, despite depletion of resident peritoneal cells, no difference in dye extravasation was seen in cyclophosphamide-versus saline-treated animals. Those compounds which inhibited iLTC, also inhibited dye extravasation with similar potency. Cyproheptadine, however modestly, inhibited dye extravasation (33%) without altering iLTC, production. Neutrophil infiltration was also monitored and was significantly inhibited by the oral administration of phenidone (73%) and SK&F 104493 (81%). This model provides a reliable method to evaluate in vivo inhibition of leukotriene biosynthesis and the associated inflammatory response induced by a pathophysiologically relevant stimulus.