In order to determine the characteristics and the course of diseases treated with long-term plasmapheresis (e.g., more than 25 plasma exchanges), we retrospectively studied 850 patients who underwent plasmapheresis. Long-term plasma exchange was prescribed to 38 patients who failed to respond to conventional therapy; cryoglobulinemias, peripheral neuropathies and monoclonal gammopathies were their most frequent underlying diseases. Improvement was noted in 65.8% cases. Only minor side effects were observed and the risk/benefit ratio for such therapy was excellent.