Male Dunkin Hartley guinea pigs, actively sensitized to ovalbumin (OA) and pretreated with mepyramine (1 mg/kg i.p.), were challenged with OA as an aerosol. Histological analysis of the lung for eosinophils (EOs) showed significant accumulations in the submucosa of the airways (8 h: 1,477.3 ± 43 EOs/mm² airway, n = 3, p < 0.01), after antigen challenge compared to saline control (478.6 ± 104 EOs/mm² airway, n = 4). Pretreatment with both mepyramine and cimetidine (10 mg/kg i.p.) did not affect this response. Aerosolization of OA to unsensitized guinea pigs resulted in no significant accumulation of EOs (360.2 ± 49 EOs/mm² airway, n = 4) when compared with the saline-challenged sensitized control group. Pretreatment with the leukotriene (LT)D₄ receptor antagonist MK-571 (1 mg/kg p.o.) significantly inhibited the OA-induced EO migration (95 ± 5% inhibition, n = 5, p < 0.01) compared to vehicle in the presence of mepyramine and cimetidine, while indomethacin (3 mg/kg p.o., n = 4) had no effect. Aerosolization of synthetic LTC₄ (0.3–30 μg/ml) resulted in a dose-dependent migration of EOs into the submucosal layer over 8 h, reaching significance at the 10-μg/ml dose, with comparable results obtained with LTD₄. Pretreatment of animals with MK-571 (1 mg/kg p.o.) before LTC₄ and LTD₄ aerosol results in inhibition of the response in both cases, suggesting that this effect may be mediated through the LTD₄ receptor. We conclude that peptide LTs produce eosinophilia in the airways of the guinea pig.