Dendritic cells (DC) play an important role in the induction of T-cell responses. We hypothesize that the hampered antiviral T-cell response in chronic hepatitis B patients is a result of impaired dendritic cell function. In this study, we compared the number, phenotype and functionality of two important blood precursor DC, myeloid DC (mDC) and plasmacytoid DC (pDC), of chronic hepatitis B patients with healthy volunteers. No differences in percentages of mDC and pDC in peripheral blood mononuclear cells were observed between chronic hepatitis B patients and healthy controls. The allostimulatory capacity of isolated and in vitro matured mDC, but not of pDC, was significantly decreased in patients compared to controls. Accordingly, a decreased percentage of mDC expressing CD80 and CD86 was observed after maturation, compared to controls. In addition, mDC of patients showed a reduced capacity to produce tumor necrosis factor β£ after a stimulus with synthetic double-stranded RNA and interferon β₯. Purified pDC from patients produced less interferon β£, an important antiviral cytokine, in response to stimulation with Staphylococcus aureus Cowan strain I than pDC isolated from controls. In conclusion, mDC and pDC are functionally impaired in patients with chronic hepatitis B. This might be an important way by which hepatitis B virus evades an adequate immune response, leading to viral persistence and disease chronicity. (HEPATOLOGY 2004;40:738 -746.) H epatitis B virus (HBV) infection represents an enormous health problem worldwide. More than 350 million people are chronically infected with HBV and are at risk to develop liver cirrhosis or hepatocellular carcinoma. Until now it is unclear why an individual develops a chronic carrier state. However, an inadequate immune response of the host is thought to play a critical role in the chronicity of the infection. 1 To recover from an acute HBV infection, both a strong humoral and a strong cellular immune response are required. During an acute infection, patients exhibit a multispecific and polyclonal cytotoxic T-cell (CTL) response and a strong type-1 T helper cell response. 2,3 Such HBV-specific T-cell responses are generally undetectable in chronic patients. 4,5 Dendritic cells (DC) represent the most potent antigen-presenting cells and thus play an important role in the induction of specific T-cell responses. 6 Functional defects in DC could therefore be an important mechanism of the virus to evade host immune responses. In several chronic viral infections, such as human immune deficiency virus 1 and hepatitis C, impaired function of DC has been demonstrated. [7][8][9][10][11] For HBV, evidence of an impaired DC function in chronic patients exists as well. 12,13 Data on the functionality of DC in chronic HBV patients were obtained with in vitro-generated monocyte-derived DC (moDC). Recently, Osugi et al. showed several differences between moDC and the myeloid DC present in vivo. 14 Therefore, it would be more accurate to isolate and