Dithranol is highly effective in the treatment of psoriasis. The drug inhibits keratinocyte hyperproliferation, granulocyte function and, in addition, may exert an immunosuppressive effect. Free radicals, histamine, eicosanoids and platelet-activating factor have been shown to be involved in dithranol-induced dermatitis, and the oxidation products of the drug are responsible for the staining. Our experimental data suggest that extracellularly generated oxygen free radicals are responsible for both the antipsoriatic and irritative effect of the drug. Furthermore, we could recently provide evidence that extracellularly generated superoxide anion radical also induces an active adaptation mechanism resulting in increased tolerance to dithranol upon repeated application. This adaptive process may explain the requirement for increasing dithranol concentrations to maintain the antipsoriatic efficacy, and also the beneficial effect of other antipsoriatic modalities such as UV-B on dithranol-induced dermatitis. The recognition of this adaptive mechanism may open future prospects to overcome some limitations concerning the practical use of dithranol.