In patients with chronic hepatitis C, the influence of the genetic heterogeneity of the hepatitis C virus (HCV) on the progression of liver disease and on the responsiveness to interferon therapy is a matter of controversy. In this study we evaluated the genetic complexity of HCV by single-strand conformation polymorphism (SSCP) analysis of amplicons from the hypervariable region 1 (HVR1) in 168 patients with chronic genotype 1b HCV infection, of whom 122 received a single course of interferon therapy (3 MU, three times weekly for 6 months). No correlation was observed between the degree of genetic complexity of HCV (indicated by the number of bands in the SSCP assay) and patient age, serum alanine aminotransferase activity, or serum HCV-RNA concentration, measured by competitive polymerase chain reaction. HCV genomic complexity was not related to gender nor to the presumed source of infection. The number of SSCP bands detected in serum samples from patients with chronic hepatitis, either mild (8.1 ± 3.9), moderate (8.0 ± 3.3), or severe (9.2 ± 3.3), and in patients with liver cirrhosis, either compensated (8.0 ± 2.9), decompensated (6.3 ± 2.9), or with superimposed hepatocellular carcinoma (9.5 ± 2.9), was similar. The number of SSCP bands detected in patients with sustained response (7.5 ± 3.9), transient response (8.3 ± 2.9), or no response (8.2 ± 3.6) to interferon administration was similar as well. These observations suggest that the genetic complexity of hypervariable region (HVR1) of HCV, as estimated by SSCP analysis, is not related to the severity of liver injury nor to the type of response to interferon therapy. Thus, information offered by SSCP analysis of HVR1 of HCV in chronic HCV genotype 1b infection does not appear to be useful in the clinical management of these patients.