During isolated limb perfusion with TNFα and melphalan, patients are exposed to high concentrations of these drugs in the perfused limb and low concentrations in the systemic circulation. The clinical application of this technique, in the treatment of locally advanced melanoma and sarcoma, made it possible to study the immunomodulatory effects of exposure to TNFa and melphalan in man. Effects of longterm exposure to cytokines were investigated in mesothelioma-patients treated with intrapleural TNFα and melanoma-patients treated with subcutaneous IFNα