Hepatitis C virus (HCV) genotype 1b is the most prevalent in Argentina. As observed in most HCV-genotype 1b described previously worldwide, the population analyzed in this work is growing at exponential rate. Ten out of 22 samples tested comprise a well-defined cluster. This new cluster appears to be highly susceptible to therapy with non-pegylated interferon plus ribavirin (80% rate of sustained response). The comparative analysis of amino acid sequences yielded a characteristic pattern for responder samples defined by amino acids S75, V147, V158 (Core region) and AC2217-8 (NS5A region). In conclusion, this study describes the epidemic spread of genotype 1b in Buenos Aires, Argentina, and shows the emergence of a new cluster that would result from a founder effect of an unusual sequence or a quasispecies variant that evolved through the time. This cluster, which appears to be highly susceptible to therapy, suggests that the virus itself might be more important than individual patient characteristics when responding to treatment.