To determine the role of antigen presenting cells (APCs) during hepatitis C virus (HCV) infection, murine lymphoid dendritic cells (LDCs), the most potent APCs, were transfected with HCV genes using adenovirus vector-mediated gene transfer. At a multiplicity of infection (MOI) of 100, more than 90% of the transfected LDCs expressed the HCV genes (encoding core-E2 region). The stimulatory capacity of these LDCs (LDC-AxCA327) in the allogeneic mixed leukocyte reaction (Allo MLR) was significantly lower (P < 0.01) than that of LDCs infected with control adenovirus vector lacking the HCV genes (LDC-Axw1). LDC-AxCA327 also produced significantly lower levels of IL-12 than LDC-Axw1 (P < 0.05). These findings suggest that the inadequate APC capability of LDCs that express HCV genes is related to immunopathology during HCV infection and that IL-12 appears to be involved in this process.