Chronic hepatitis C virus (HCV) infection is associated with weak CD4+ T-helper type 1 reactivity and enhanced interleukin-10 production to HCV antigens. Here we demonstrate in vitro that monoclonal antibody-induced blockade of IL-10 receptor (IL-10R) generates a favorable balance of CD4+ T-cell responses to HCV. The addition of anti-IL-10R to mononuclear cells leads to a dose-dependent increase of T-cell proliferative response to HCV core, non-structural proteins 3 and 4. In competition experiments, anti-IL-10R reversed the inhibitory effect of IL-10 on HCV-specific T-cell proliferation. Furthermore, the blockade of IL-10R altered the balance towards type 1 antiviral T-cell reactivity with an increased frequency of HCV-specific IFN-gamma producing T-cells and IFN-gamma secretion. The impact of IL-10R blockade on T-cell reactivity to HCV demonstrates the major role of IL-10 in suppressing antiviral T-cell responses. Blocking IL-10 activity may be a useful immunotherapy approach to enhance the efficacy of antiviral treatment in chronic hepatitis C.