The essential oil of Australian tea tree (Melaleuca alternifolia) has been investigated for skin irritancy using an occlusive patch test on 25 human subjects for 21 days. 1,8-Cineole, the constituent reported as being responsible for tea tree oil skin irritancy, was similarly tested. Irritancy was not detected from any of eight preparations containing pure cineole in concentrations of 0.0, 3.8, 8.0, 12.0, 16.0, 19-9, 24.0 and 28.1% in soft white paraffin. Eight tea tree oil preparations containing similar concentrations of cineole did not show skin irritation when tested at 25% in soft white paraffin. However, 3 of 28 panelists were withdrawn from the trial because of a severe allergic (as distinct from irritant) response to tea tree oil. These subjects were then tested with either pure tea tree oil major constituents or crude fractions. One panelist showed a strongly positive reaction to α-terpinene and all three reacted (two strongly) to two sesquiterpenoid fractions. None showed allergic response to α-pinene, β-pinene, limonene, p-cymene, 1,8-cineole, γ-terpinene, terpinolene, terpinen-4-ol or α-terpineol in 24-28 h. Three positive reactions occurred to a sesquiterpene hydrocarbon fraction, and one to a sesquiterpene alcohol fraction. The significance of these human tests with the topical application of tea tree oil products is discussed and methods for the minimization of allergens are suggested.