Objective: To examine the effects of topical therapy with Mahonia aquifolium on the expression of pathogenetically relevant molecules in psoriatic skin by immunohistochemistry. Study Design: Prospective-randomized, half-side comparison study with subsequent immunohistochemical assessment of biopsies. Methods: The study areas were treated with Mahonia aquifolium ointment 3( daily and with dithranol in rising concentrations 1( daily, respectively. Biopsies of lesional skin from the test areas were carried out in 49 patients a) prior to therapy and b) 4 weeks after the start of therapy. Immunohistochemical stainings were performed with the following monoclonal antibodies: anti-ICAM-1, -CD3, -HLA-DR, -keratin 6, -keratin 16, -Ki-67. Evaluation of staining was made by two independent examiners using established semiquantitative scores. Results: Marked staining with all of the cited monoclonal antibodies was observed in the lesional skin prior to therapy. After 4 weeks of therapy there was a marked reduction in the expressions of ICAM-1, CD 3, HLA-DR and keratin 6 and 16. There were significantly greater reductions of ICAM-1, CD3, and HLA-DR at sites treated with dithranol. The expression of Ki-67 was not reduced by either therapy. Conclusions: These results indicate efficacy of Mahonia aquifolium and dithranol in psoriatic skin both on cellular cutaneous immune mechanisms and on the hyperproliferation of keratinocytes. The effect of dithranol appears to be more potent than that of Mahonia aquifolium.