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Background: Tumor necrosis factor-· (TNF-·) is involved in the pathogenesis of chronic active hepatitis C. Polymorphisms in the promoter region of the TNF-· gene can alter the TNF-· expression and modify the host immune response. The present study aimed at the correlation of the G308A TNF-· polymorphism with the response to antiviral combination therapy in chronic hepatitis C. Patients and Methods: 62 patients with HCV and 119 healthy unrelated controls were genotyped for the G308A TNF-· promoter polymorphism. The patients received 3 ! 3 million units of interferon alfa-2a and 1,000-1,200 mg ribavirin daily according to their body weight. A response was defined as absence of HCV-RNA and normalization of S-ALT after 6 months of combination therapy. Results: With respect to the allele and genotype frequency, a significant difference was not observed between controls and patients with chronic hepatitis C. Furthermore, such a difference was also not observed if responders and non-responders to antiviral therapy were compared. Conclusions: The promoter polymorphism of the TNF-· gene investigated herein is equally distributed in healthy individuals and patients with hepatitis C and does not seem to predict the response to therapy with interferon alfa-2a and ribavirin.