Objective: To examine the effect of topically applied tea tree oil (TTO) on histamine-induced oedema in the ears of mice. Methods and results: For BALB/c mice, 10 μl undiluted TTO applied immediately after, but not 30 min before intradermal injection of 600 μg histamine in 10 μl, significantly suppressed oedema development. TTO applied after histamine injection also suppressed histamine-induced oedema in C57/BL6 mice. TTO applied immediately after intradermal injection of compound 48/80 (200 μg in 10 μl saline) also significantly reduced ear swelling. TTO suppressed histamine-induced oedema to the same extent in capsaicin-treated (neuropeptide-depleted) and control mice which suggests that TTO does not inhibit histamine-induced oedema by regulating the activity of peripheral sensory neurons. Terpinen-4-ol, the major water-soluble component of TTO, was equivalent in potency to TTO in the suppression of histamine-induced ear swelling. Conclusion: Topical application of TTO, and in particular terpinen-4-ol, may be effective in controlling histamine-induced oedema often associated with Type I allergic immediate hypersensitivities.