Hepatitis B virus (HBV) genotypes B and C are most prevalent in China and genotype B is found exclusively in recombination with the pre-C/C gene of genotype C. We investigated whether there is a difference in clinical relevance between the two genotypes sharing the same pre-C/C gene. Thus, we determined the genotype of HBV among consecutive HBeAg-positive patients with tailored interferon-alpha (IFN-alpha) therapy, and the demographic, baseline clinical characteristics and treatment results were compared between them. The median values of alanine transaminase (ALT) were 4.5 and 5.0 times the upper limit of normal (P = 0.419), HBV-DNA levels were 1.4 x 10(7) and 1.5 x 10(7)copies/mL (P = 0.829), mean scores of necroinflammatory histological activity 9.8 and 10.44 (P = 0.105) and fibrotic activity 2.64 and 2.86 (P = 0.227) in genotype B and C patients, respectively. The end-of-treatment response was 42.7% and 39.0% (P = 0.531) with mean tailored treatment months of 8.28 and 9.34 (P = 0.160), and the sustained response 43.4% and 37.5% (P = 0.31) at the end of a 12-month follow-up period in genotype B and C patients, respectively. These results remained similar when follow-up was extended to nearly 3 years. In conclusion, no significant differences in clinical characteristics and response to IFN-alpha between genotypes B and C were found, probably, because both types shared a common pre-C/C encoding region.