BACKGROUND: The role of T-cell immunity in chronic hepatitis C virus (HCV) infection remains controversial. As in HIV infection, virus replication could drive or be contained by T-cell immunity. We have examined the effect of HIV coinfection and of suppression of HCV replication with therapy on HCV-specific T-cell responses. PATIENTS AND METHODS: Thirty-five patients with chronic hepatitis C (17 coinfected with HIV) initiating anti-HCV therapy were analysed. HCV-specific responses were assessed at different time points using intracellular interferon-gamma staining in response to a panel of overlapping peptides comprising E2, NS3, NS5a and NS5b HCV proteins. RESULTS: At baseline, HCV-specific responses were significantly lower in HIV-coinfected patients. At week 12 of therapy, CD8+ T-cell responses against all HCV proteins significantly decreased in HCV-monoinfected patients and this was maintained throughout the follow-up period. Although the same trend occurred in the HIV-coinfected group, differences were not significant. CD4+ T-cell responses against NS3 significantly diminished in the HCV-monoinfected group, whereas in coinfected patients CD4+ T-cell responses were low at baseline and did not experience any significant variation. CONCLUSIONS: HCV-specific T-cell responses are lower in HIV-coinfected patients and vanish following complete suppression of HCV replication under successful HCV therapy, suggesting that they are dependent on continuous antiqenic stimulation.