In order to confirm the mechanism of nasal secretion mediated via a nerve reflex in guinea pigs, the secretory response from the contralateral side was studied which was induced by local application of various stimulators. There was no difference in the nasal secretion between the contralateral and the stimulated sides when the secretion was induced by allergen, histamine, and capsaicin at lower doses. Methacholine caused a nasal secretion only on the stimulated side. Pretreatment with local anesthetic and ganglionic blockers blocked the secretory response bilaterally which was induced by allergen, histamine, and capsaicin. Antihistaminics also blocked the secretory response induced by allergen and histamine on both sides, but not the capsaicin-induced nasal secretion. Unilateral pretreatment with local anticholinergics prevented all secretory responses only on the stimulated side. Thus, exogenous and endogenous histamine released by the allergen-antibody reaction may stimulate histamine H1 receptors located in the sensory nerve endings as trigger, resulting in the secretory response mediated via a nerve reflex, while methacholine may act directly on nasal glands. Ketotifen and azelastine, which are chemical mediators releasing inhibitor with antihistaminergic activity, prevented the nasal secretion induced by histamine and allergen. On the other hand, disodium cromoglycate, amlexanox, and tranilast had only a slight effect on the allergen-induced nasal secretion. The secretory response on the contralateral side induced by various stimulators would be useful in the in vivo evaluation of anti-allergic drugs to demonstrate the difference in their modes of action.