Molecular epidemiologic studies have indicated the possible existence of mixed infection of different hepatitis B virus (HBV) genotypes in chronic hepatitis B (CH-B) carriers, but the effect of dual HBV genotype B and C infection on the efficacy of lamivudine therapy remains unclear. We report four CH-B patients with dual HBV genotype B and C infection and acute exacerbation who received lamivudine monotherapy for about 18 months. None of them had achieved a sustained response at the end of the 18-month trial of treatment.