Tumor necrosis factor (TNF) an inflammatory cytokine expressed by human fetal liver cells (HFLCs) following infection with cell culture-derived hepatitis C virus. TNF has been reported to increase entry of HCV pseudoparticles into hepatoma cells and inhibit signaling by interferon alpha (IFNA), but have no effect on replication of HCV RNA. We investigated the effects of TNF on HCV infection of and spread among Huh-7 hepatoma cells and primary HFLCs.