Cysteinyl leukotrienes (CysLTs: LTC₄, LTD₄, and LTE₄) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. Because treatment with a CysLT₁ receptor antagonist and a 5-lipoxygenase inhibitor modified allergen-induced nasal blockage in patients with allergic rhinitis, and CysLTs were detected in nasal cavity lavage fluid, it has been suggested that CysLTs act as significant inflammatory mediators in allergic rhinitis. The role of CysLTs was evaluated in our experimental allergic rhinitis model in sensitized guinea pigs which shows biphasic nasal blockage, sneezing and nasal hyperresponsiveness to LTD₄ induced by repetitive inhalation challenge with Japanese cedar pollen. In this model, the CysLT₁ receptor antagonist pranlukast suppressed the late-phase nasal blockage but not early blockage and sneezing. Nasal hyperresponsiveness (nasal blockage) to LTD₄ was largely blocked by pranlukast, naphazoline, and N^ω-nitro-L-arginine-methyl ester. The results demonstrate that nasal blockage induced by CysLTs is mainly due to dilatation of nasal blood vessels, which can be induced by the nitric oxide produced through CysLT₁ receptor activation. On the other hand, when pollen inhalation challenge was performed in the presence of nasal hyperresponsiveness, antigen-induced biphasic nasal blockage and sneezing were considerably enhanced and CysLTs contributed to both symptoms, suggesting that nasal hyperresponsiveness induces aggravation of antigen-induced nasal symptoms. The results presented in this study further suggest that our model is a good representative of human allergic rhinitis and offer evidence that CysLTs are chemical mediators mainly responsible for allergic nasal symptoms.