NATURAL HISTORY OF HEPATITIS C-INFECTION AND VIRAL CHARACTERISTICS: Hepatitis C-virus (HCV) infection is a major cause of non-A, non-B-hepatitis and, additionally, is associated with liver cirrhosis and hepato-cellular carcinoma. The high degree of chronificity of HCV-infection is reasonable due to antigenic variability of neutralizing epitopes leading to incomplete immunoresponse with subsequent virus persistence. Besides genetic variants of HCV within a virus population (quasispecies nature of HCV), different genotypes are classified being genetically and phenotypically distinct, and geographically restricted in part. Genotyping of HCV is not only important for phylogenetic and epidemiological studies, but also a predictive marker for pathogenesis and therapy. VIRAL PREDICTORS OF HCV THERAPY: In a meta-analysis of 18 therapeutical studies of chronical HCV infections, genotype 1 and high levels of viremia determined markedly the response to interferon therapy. In this context, clinical trials have proven the effect of a combined therapy with interferon and ribavirin. Especially patients with HCV genotype 1 or high levels of viremia had a real benefit from combined antiviral therapy in comparison to monotherapy with interferon. CONCLUSION AND FUTURE CONCEPTS: Besides recent concepts improving the therapeutical response to HCV infection, further effort is necessary to develop more successful strategies for eradication of hepatitis C virus. In this context, variations of interferon therapy should be evaluated (e.g. higher and daily doses, longer duration of interferon therapy, "retarded" interferon (PEG-IFN). In addition, new therapeutical concepts should be performed including a combination of interferon with other known antiviral agents (amantadine), a combination with immunomodulators (GM-CSF, thymosin alpha 1), the development of new antiviral agents (inhibitors of viral proteases, helicases and polymerases) and the exploration of anti-viral, molecular strategies (specific ribozymes, antisense oligonucleotides and DNA-vaccination). Nevertheless, the development of an effective vaccination should be the most important challenge for the future.