HCV virus infections have become a serious epidemiological problem throughout the world. Hepatitis C therapy includes the administration of IFN-alpha and ribavirin, but results in the complete eradication of HCV viremia in only 30% of patients. TNF-alpha is one of the factors involved in hepatitis C pathogenesis and the results of therapy. In this study, we present the results of applying real-time RT-PCR for assessing the TNF-alpha mRNA level in the peripheral blood of patients treated with IFN-alpha and ribavirin. We found the TNF-alpha mRNA level to be higher in HCV-infected patients compared with healthy controls when analyzed after 4 weeks (p = 0.001) and 3 months (p = 0.003) of IFN-alpha/RIBA therapy. The pretreatment level and the level after six months of therapy were not significantly different from the level of healthy controls. There were no significant differences in TNF-alpha mRNA levels between patients who responded to anti-HCV therapy, resulting in a decrease in HCV viremia below detection limit over 6 months and patients whose HCV RNA was not eliminated (p = 0.881). These results indicate that there is a transient increase of TNF-alpha gene expression during anti-HCV therapy. This fact may be connected with the host organism's response to IFN-alpha/RIBA therapy.