Objective To compare the long-term efficacy of a dose of 3 million units (MU) of r-IFN alpha 2a (IFN-α 2a) three times a week (t.i.w.) for 6 months with a starting dose 6 MU for 3 months and subsequent reduction to 3 MU t.i.w for further 3 months.Methods Sixty-eight serological and histological chronic hepatitis C patients with elevated serum alanine aminotransferase (ALT) were enrolled and randomized into two groups. Sixty-three patients were completed with full course of treatment. Five patients were withdrawn from trial (2 due to personal reasons and 3 due to adverse drug reactions during treatment). Thirty patients received 6 MU IFN-α 2a t.i.w., 3 months followed by 3 MU t.i.w. for another 3 months (Group A). Thirty-three patients received 3 MU IFN-α 2a t.i.w. for 6 months (Group B).Results The sex, age, baseline serum bilirubin, ALT and aspartate aminotransferase (AST) levels were matched in both groups. At the end of the 6th month, the complete and partial response rates in Group A were 60.0% and 16.7% respectively, and the clearance of serum HCV-RNA was 53.3%. In Group B, the complete and partial response rates were 72.7% and 6.1% respectively, and the clearance of HCV-RNA was 61.3%. The patients were followed up for 6,12, and 18 months after stopping treatment. In Group A, the rates of complete normalization of ALT and clearance of serum HCV-RNA at 24 months were 50.0% and 60.0% respectively. In Group B, the rates of normalization of ALT and clearance of HCV-RNA at 24 months were 54.4% and 41.9% respectively. The efficacy between the two groups showed no statistically significant difference. The response rates of treatment were similar to those in the patients with HCV genotype 1b and 2a. Six patients (10.8% of the study population) developed neutralization antibodies to IFN-α 2a during treatment, and four of them were responded to the treatment. Adverse drug reactions (ADR), were common, but most of them were tolerable, and the incidence of ADR was in both groups, but the severity was higher in Group A.Conclusions IFN-α 2a is effective in the treatment of Chinese patients with chronic hepatitis C. The sustained response rates and adverse drug reactions among two dose schedule groups are similar.