Double-filtration plasmapheresis (DFPP) selectively removes high molecular weight substances including hepatitis C virus (HCV). Four live donor liver transplantation (LDLT) recipients with HCV received combination therapy with low-dose interferon (IFN) and ribavirin with DFPP. Three patients underwent this therapy for prophylaxis of HCV recurrence, and one for treating fibrosing cholestatic hepatitis (FCH). The combination therapy and DFPP decreased HCV RNA levels to 8.2% +/- 2.9% and 0.7% +/- 0.5% by the 5th and 30th day of treatment, respectively. Three patients who underwent DFPP for prophylaxis showed no evidence of HCV recurrence for >1 year after treatment. The patient whose graft showed FCH, recovered dramatically after the DFPP treatment. DFPP appeared to be effective in reducing HCV viremia and preventing HCV recurrence in patients with high HCV RNA levels after LDLT. Moreover, it may become a rescue therapy for FCH in a liver transplant recipient with hepatitis C.