AIM: To assess the efficacy of ribavirin monotherapy in patients with biochemical relapse after combination therapy.METHODS: Twenty-four weeks of ribavirin monotherapy was given to biochemical relapsers of end treatment biochemical responders within 6 mo after combination therapy, including non-responders with HCV-RNA level ≤0.2 Meq/mL and end treatment virologic responders (ETVRs) with or without reappearance of HCV-RNA.RESULTS: Sixty-two chronic HCV-infected patients completed 24 wk of interferon-α plus ribavirin combination therapy. Fifty patients (80%) achieved end treatment biochemical response including 16 non-responders and 34 of 36 ETVRs. Twenty-six patients (41.9%) were nonresponders. Ribavirin monotherapy was given to 20biochemical relapsers including 12 non-responders with HCV-RNA levels ≤0.2 Meq/mL, four of eight HCV-RNA reappearing ETVRs, and four HCV-RNA negative ETVRs.After 24 wk of ribavirin monotherapy, one of 12 nonresponders, two of four HCV-RNA reappearing ETVRs and all four RNA-negative biochemical relapsers of ETVRs showed sustained virologic response. Two of 12monotherapy treated non-responders showed persistent normalization of liver function test. In total, 50% (31/62)of patients achieved sustained virologic response.CONCLUSION: Resumption of ribavirin monotherapy in ETVRs at signs of viral rebound and recurrent biochemical abnormalities rather than continuation of monotherapy appears to be the key to success of ribavirin monotherapy after interferon-related combination therapy.