This study investigated endogenous mediators involved in mosquito allergy-associated itching in mice. An intradermal injection of an extract of mosquito salivary gland elicited marked scratching in sensitized mice. The 5-lipoxygenase inhibitor zileuton (100 mg/kg), the 5-lipoxygenase activating peptide inhibitor MK-886 (10 mg/kg), and the glucocorticoid betamethasone 17-valerate (3 mg/kg) inhibited the scratching. The scratching was not affected by the cyclooxygenase inhibitors indomethacin and ketoprofen, the TP prostanoid receptor antagonist SQ-29548, the leukotriene B₄ antagonist ONO-4057, the cysteinyl leukotriene antagonist pranlucast, the leukotriene D₄ antagonist MK-571, the platelet-activating factor antagonist CV-3988, the nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester, the H₂ histamine-receptor antagonist cimetidine, the H₁ histamine-receptor antagonist terfenadine plus cimetidine, and cypoheptadine that blocks the 5-HT_1/2 serotonin receptors. Zileuton (100 mg/kg) inhibited the increased activity of the cutaneous nerve branch induced by an intradermal injection of the extract, suggesting the peripheral action. Zileuton and MK-886 (10 and 100 μM) did not affect high K⁺-induced increase in intracellular Ca²⁺ concentration in cultured dorsal root ganglion neurons. The results suggest that 5-lipoxygenase metabolite(s) other than leukotriene B₄ and cysteinyl leukotrienes are involved in mosquito allergy-associated itching.