Abstract: To investigate the relationship between intrahepatic cytokine expression and interferon (IFN) response in chronic hepatitis C [CH(C)], interleukin (IL)-1ß,-2,-4,-6,-8, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and TNF-ß mRNAs were investigated semiquantitatively by reverese transcription polymerase chain reaction using serial liver biopsies taken before and after IFN-α treatment from 24 patients with CH(C), including 12 responders and 12 non-responders. Before IFN treatment, IL-2, TNF-ß, IFN-γ and IL-8 mRNA were associated with severe hepatitis activity whereas IL-4 mRNA was associated with weak hepatitis activity, regardless of IFN response. IL-2, TNF-ß and IFN-γ mRNAs were significantly greater in IFN non-responders. After IFN treatment a complete response to IFN was significantly associated with the disappearance of these pro-inflammatory cytokines, whereas non-responders retained the expression of cytokine mRNA as before IFN treatment. Our results indicated that IFN-α treatment may modulate the intrahepatic cytokine network, and this may be one mechanism of IFN-α that reduces hepatitis activity, aside from an anti-viral effect. A difference in cytokine network may be involved in IFN response in CH(C).