T cell immune responses may be important for the elimination of chronic hepatitis C virus (HCV) infection during antiviral treatment. In the present study, the kinetics of T cell responses to HCV antigens (NS3-4 and core) were prospectively assessed and were correlated with virologic outcome in 31 patients with chronic HCV infection undergoing peginterferon-α2a/ribavirin therapy. NS3-4—directed T helper cell type 1 (Th1) responses were detected in 77% of patients with a significant decline in viremia at treatment week 4 but were not detected not in those with a slower viral decline. The detectability of NS3-4—directed Th1 responses was associated with faster viremia clearance, was short-lived, and did not seem to be associated with the final treatment outcome.