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Background: Prurigo nodularis shows intense itching nodules, which are often persistent and therapy refractory. Histological alterations include fibrosis of collagen fibers and presence of inflammatory infiltrate, which partly explains the clinical persistence of lesions. Inflammatory cells may directly contribute to induction and maintenance of pruritus at nerve fibers. Cyclosporine microemulsion (ME) suppresses the migration and proliferation of inflammatory cells and may thereby interfere with pathogenesis of prurigo nodularis. The aim of this investigation was to assess the antipruritic efficiency of cyclosporine ME in therapy of prurigo nodularis., Patients and Methods: 14 patients with prurigo nodularis of diverse origin and failure to previous therapy were treated with oral cyclosporine ME (3 to 5 mg per kg daily). Blood pressure, liver enzymes, renal function and differential blood count were monitored., Results: In 13 of 14 prurigo patients (92.9 %) there was a significant response to monotherapy with cyclosporine ME. The maximal antipruritic effect occurred after 2 weeks to 12 months. Prurigo nodules also healed during therapy. Seven patients (50.0 %) described side effects. In one case the therapy was stopped., Conclusions: Oral cyclosporine ME is an effective therapy for prurigo nodularis of diverse origin. It appears to function by inhibiting dermal inflammatory cells.