The aim of this study was to examine whether 78 week course of interferon (IFN) retreatment could improve the beneficial effect of IFN in chronic hepatitis C patients compared with 52 week course of IFN retreatment. Inclusion criteria were biopsy-proven chronic hepatitis, serum HCV-RNA level of more than 1 Meq/ml, HCV-genotype 1b, abnormal serum alanine aminotransferase (ALT), and transient negative conversion for HCV-RNA during the initial course of IFN therapy. Forty-one patients were randomly assigned to two groups, receiving total doses of: 1410 MU for 52 weeks (a 52 week-group: n=20), or 1995 MIU for 78 weeks (a 78 week-group: n=21). But three patients (one in the 52 week-group and two in the 78 week-group) were withdrawn from the study due to a transfer, refusal after randomization, and occurrence of malignant lymphoma before IFN retreatment, respectively. Therefore remainder 38 patients were studied about efficacy of IFN administration. A virological response (VR) to IFN therapy was defined as HCV-RNA negativity by the reverse transcription nested polymerase chain reaction both 3 and 6 months after the completion of IFN retreatment. A biochemical response (BR) was defined as normalization of ALT but positive HCV-RNA both 3 and 6 months after the cessation of IFN therapy. According to these criteria, VR was 36.8% (7/19) in the 52 week-group and 21.1% (4/19) in the 78 week-group. BR was 5.3%(1/19) in the 52 week-group and 21.1% (4/19) in the 78 week-group. There was no significant difference between the 52 week-group and the 78 week-group with respect to the effect of IFN. We conclude that 52 week course of IFN retreatment may be a sufficient strategy if patients, who have HCV-genotype 1b and high virus load, show negative HCV-RNA and normal ALT level during the first IFN therapy.