Removal of cryoglobulins by plasma exchange is now an accepted therapy. Cryoglobulins are circulating complexes that can deposit on small vessels and cause limited or extensive tissue injury. There are 3 major classes of cryoglobulins. Type I cryoglobulins are monoclonal and are detected in a variety of lymphoproliferative disorders. Type II cryoglobulins are mixed containing monoclonal and polyclonal IgG or IgM molecules. Type III cryoglobulins are also mixed and contain polyclonal IgG. Type II cryoglobulins are largely caused by hepatitis C virus infection; hence, they are the most common of the 3 types. In hepatitis C, cryoglobulins are linked to glomerular immune complex injury, often times accompanied by vasculitis of the skin, nerves, and other vital organs. Immediate removal of cryoglobulins by plasma exchange is an effective short-term treatment that can complement more-specific therapies. Plasma exchange has also been used to remove other circulating nephrotoxic agents such as antiglomerular basement antibodies that cause Goodpasture's syndrome, protease inhibitor autoantibodies that cause thrombotic thrombocytopenic purpura, and antiglomerular factors that cause some types of focal glomerulosclerosis.