The mechanisms of alcohol-induced immunosuppression include defects in innate and adaptive immune responses. Monocytes and dendritic cells (DCs) link innate and adaptive immune responses as they recognize viral antigens and induce antigen-specific T-cell activation. We investigated the effects of alcohol on antigen-presenting cell functions. Acute alcohol consumption by healthy volunteers (vodka, 2 ml/kg) resulted in significantly reduced antigen-presenting cell function of monocyte-derived DCs. Reduced allostimulatory capacity of DCs treated with alcohol in vitro correlated with decreased co-stimulatory molecule (B7.1 and B7.2) expression, as well as with reduced interleukin (IL)-12 and increased IL-10 concentrations, in mixed lymphocyte cultures. Dendritic cells recognize viral antigens in hepatitis C virus (HCV) infection, and HCV disease is accelerated in alcohol-dependent individuals. For patients with chronic HCV infection, we found reduced allostimulatory capacity of myeloid DCs. Furthermore, DC function was reduced by in vitro alcohol treatment of DCs obtained from HCV-infected patients, supporting the suggestion that viral factors and alcohol may interact to doubly suppress DC functions. We found that induction of maturation with lipopolysaccharide could not fully ameliorate the reduced DC allostimulatory capacity caused by alcohol treatment, HCV infection, or their combination. In addition, soluble factors in the supernatants obtained from mixed lymphocyte cultures containing alcohol-treated DCs or DCs obtained from HCV-infected patients could transfer inhibition of T-cell proliferation in cultures containing DCs obtained from healthy volunteers. Anti-IL-10 neutralizing antibody ameliorated the reduced mixed lymphocyte reaction containing DCs obtained from HCV-infected patients, whereas exogenous IL-12, but not anti-IL-10, treatment ameliorated the reduced T-cell proliferation induced by alcohol treatment of DCs obtained from healthy volunteers. Our results support the suggestion that both acute alcohol intake and in vitro alcohol treatment inhibit DC antigen-presenting cell function and support the hypothesis that viral factors interact with alcohol to reduce DC functions in HCV infection.