Rheopheresis is a specifically designed application of double filtration plasmapheresis, for extracorporeal treatment of microcirculatory disorders. Safety and efficacy of Rheopheresis for wound healing and skin oxygenation were investigated in patients with critical limb ischemia. Twelve patients of Fontaine stage III-IV were treated with a series of 10 Rheopheresis sessions over 17 weeks. Transcutaneous oxygen pressure (tcpO(2)) and ankle-brachial index (ABI) were repeatedly determined to monitor the effects of the Rheopheresis treatment series on microcirculation and skin blood flow. Laboratory parameters of blood rheology were measured in addition to safety parameters and course of the pain syndrome was documented. In four patients (baseline Fontaine stage III) Rheopheresis was associated with an improvement of Fontaine stage, a pronounced increase in tcpO(2) and complete regression of the rest pain. As an adjunct therapeutic option, Rheopheresis may preserve a functional lower extremity, delay amputation or reduce the extent of amputation.