The genomic heterogeneity of hepatitis C virus (HCV) was addressed in the different phases of HCV infection. Viral sequences of the HVR-1 and NS5a regions were obtained by reverse transcription polymerase chain reaction from plasma samples of two patients with acute type-C hepatitis and two patients with chronic infection treated with interferon. The data indicate that in primary infection different degrees of genomic heterogeneity in biologically important viral regions might be associated with different clinical outcomes.