Dithranol is established as a very successful treatment for psoriasis. Its main disadvantages are irritation and staining at sites of application. The aim of the present study was to elucidate further the mechanism of dithranol-induced irritation, in particular to what extent this is related to an impairment of the skin barrier. Dithranol 3% in cream, paste and petrolatum was applied to the forearm skin of 20 volunteers and left in situ for 1 h. Transepidermal water loss (TEWL) was measured during a period of 2 weeks following dithranol application. In addition, a visual scoring system and colorimetry were used to assess erythema. The study showed conclusively that TEWL was not affected by the application of dithranol, even though pronounced erythema occurred.