Six patients were studied to evaluate the efficacy and safety of plasma exchange (PE) in the treatment of primary biliary cirrhosis (PBC). All patients were affected by PBC at stage III-IV and presented symptoms refractory to pharmacologic therapy. Patients underwent PE for a mean period of 40 weeks (range 10-88). A mean of 33 liters (range 17-64) of plasma per patients was removed. Patients reported less fatigue (4/6), pruritus (5/5), nausea (3/3), Sjogren's syndrome (2/6), and painful neuropathy (2/3). A reduction of xanthomata was noted in one of the three affected patients. Definitive improvement was seen in the patient with Raynaud's phenomenon. A significant reduction was noted for serum cholesterol and gammaglobulins. ALT, AST, gamma-GT, alkaline phosphatase, bilirubin, prothrombin activity, AMA titers were not affected by PE. All patients suffered some mild adverse effects during PE. Two patients (IV stage) developed late edema and ascites after 34 and 44 weeks of treatment. We conclude that PE can be considered effective chronic treatment for advanced symptomatic PBC refractory to pharmacological therapy.