Genetic heterogeneity is a characteristic feature of hepatitis C virus (HCV) and it reflects selection mechanisms affecting the virus. It is considered a major factor contributing the viral persistence and drug resistance. The following work presents the preliminary results of 5'UTR and E2/HVR1 genetic variation analysis and comparison in serum and peripheral blood mononuclear cells (PBMC) of 7 patients before and during the early phase of pegylated interferon alfa (PEG-IFN-alpha) and ribavirin therapy. Single strand conformational polymorphism (SSCP) analysis revealed genetic stability of 5'UTR in all but one patient who did not respond to treatment (SVR-), where new genetic variants appeared. E2/HVR1 genetic changes were characteristic in patients displaying treatment failure (SVR-) and usually reflected fluctuations in complexity and appearance of new genetic HCV variants. Genetic changes (reduction in complexity) were found in one of three sustained virological responders (SVR+ patients). Comparatory analysis of the HCV quasispecies present in serum and PBMC showed differences in at least one analysed region in all non-responders. Presented results suggest the independent forces driving genetic changes in analysed regions. They also point out the presence of genetic compartmentalization possibly having an impact on antiviral treatment result.