A 16-week double-blind study of parallel groups was carried out in the treatment of 152 patients suffering from stable psoriasis vulgaris. Podophyllotoxin was applied once daily at three different concentrations in an ointment base, namely 0.1, 0.25 and 0.5%. One stable psoriatic lesion was selected and monitored during the study course. All three concentrations of podophyllotoxin induced a statistically highly significant improvement (p < 0.001) of the selected lesions. There was statistically highly significant difference between the treated and control lesions already after 2 weeks of treatment (p > 0.001), and this difference increased further during the study course. Eleven patients experienced adverse reactions – severe skin rash – spontaneously reported by the patients.