We investigated the interaction of immune complexes (IC) isolated from hepatitis C virus (HCV)-infected individuals with several cell lines that differentially express Fc receptors, and analyzed viral infection by the presence of HCV RNA sequences. Monocytic (U937 and Monomac-6) and lymphocytic (MOLT-4 and Jurkat) cell lines were incubated with interferon- plus phorbol myristate acetate to stimulate the expression of Fc receptors before addition of IC. Cell interaction with IC was monitored by flow cytometry. Positive cell fluorescence was detected in U937 and Monomac-6 cells [mean fluorescence intensity (MFI) 10.56+/-0.8 and 11.60+/-0.8, respectively]. Incubation of cells with monoclonal antibodies against Fc receptors for IgG before addition of IC decreased MFI in both cell lines (U937 2.1+/-0.5, Monomac-6 4.4+/-0.8, P<0.001), indicating that cell-IC interaction through these receptors was inhibited. In particular, the blockage of FcgammaRII was responsible for this effect. No binding of IC with either MOLT-4 or Jurkat cell lines was detected, which correlated with a very low Fc receptor expression. HCV RNA sequences were identified in the cells up to 120 h of post incubation with IC. These results suggest that IC can mediate entry of HCV to both U-937 and Monomac-6 cell lines mainly through the FcgammaRII.