Hepatitis B virus (HBV) infection induces a wide range of chronic liver injury. The mechanism by which HBV evades the immune surveillance system remains obscure. Plasmacytoid dendritic cells (pDCs) seem to be the major endogenous interferon (IFN)-alpha producers and represent one of the most important cell types in the regulation of antiviral innate immunity; however, the phenotype and function of pDCs in patients infected by HBV with different genotypes are yet to be determined. The aim of this study was to investigate the differences in the numbers and function of peripheral blood pDCs in the immune clearing phase of chronic HBV infection with genotypes B and C. Fifty-six patients with persistent HBV infection were included in this study, with 19 age-matched healthy subjects being used as a control group. The frequencies of pDCs were analysed by flow cytometry, and the IFN-alpha produced by peripheral blood mononuclear cells (PBMCs) after stimulation with cytidine phosphate guanosine (CpG) oligonucleotides for 24 h was determined by enzyme-linked immunosorbent assay. The genotypes of HBV were detected by polymerase chain reaction and hybridization. The results showed that the frequency and IFN-alpha-producing capacity of peripheral blood pDCs were dramatically reduced and relatively inversely correlated with the level of serum alanine aminotransferase in both groups of patients with chronic genotype B and C HBV infection. A lower reduction of IFN-alpha production by CpG-stimulated PBMCs was found in patients with genotype C than in those with genotype B in the phase of immune clearance. In conclusion, the frequency and IFN-alpha-producing capacity of peripheral blood pDCs were dramatically reduced in the immunoactive phase of chronic hepatitis B (CHB). Furthermore, the lower reduction in IFN-alpha production in patients with genotype C than in those with genotype B may correlate with the outcome of antiviral treatment in CHB patients and the progression of liver inflammation.