Background. Cost and clinically significant adverse effects are the major limiting factors of interferon (IFN) use in therapy for chronic hepatitis B virus (HBV) infection. A clinical trial was conducted in China to study the efficiency and clinical relevance of low-dose regimen of IFN treatment for chronic HBV infection and to reveal factors predicting sustained combined response. Methods. During a randomized, open-label control study, hepatitis B e antigen (HBeAg)-positive patients with chronic HBV infection (n = 230) were assigned to receive pegylated IFN-alpha-2b (1.0 mu g/kg) (n = 115) or IFN-alpha-2b 2b ( 3 MIU; n = 115) for a 24- week period. Sustained combined response was assessed 24 weeks after the completion of treatment. Results. The greater rate of HBeAg loss in the pegylated IFN-group (23%) was the only statistically significant difference between the 2 treatment arms observed at the end of follow-up. The results of the multivariate statistical analysis revealed that HBV genotype B and patient age ( <= 25 years) were 2 independent factors associated with sustained combined response. A total of 40% of patients with HBV genotype B aged <= 25-years achieved sustained combined response. Only 4 (1.7%) of 230 patients discontinued therapy because of clinically significant adverse effects. Conclusions. The choice of low-dose IFN regimen might be a relevant clinical option to reduce the cost and adverse effects of therapy for younger patients with chronic HBV infection and genotype B infection in countries where it is prevalent.