Since an efficient control of virus infections may depend on the appropriate lymphokine profile, we studied cytokine responses and CD30 induction, a recently proposed surrogate marker of type 2 cells, in 10 healthy anti-hepatitis C virus (HCV)-seropositive blood donors without viremia (group A) and in 15 patients with hepatitis C (group B). Intracytoplasmic IFN-gamma, IL-2, IL-4, and IL-10 were determined by triple-color flow cytometry in the CD3+ and CD3+/CD30+ lymphocyte subsets after stimulation of PBMC with rHCV core protein and five core-derived peptides corresponding to the four immunodominant Th epitopes C.T1 to C.T4. In group A, more type 1 cytokines were induced by the rHCV core protein and all immunodominant core peptides (p < 0.05), whereas IL-10-producing T cells were found more frequently in group B. Induction of CD30+ T cells was found almost exclusively in group B (p < 0.01). The difference in cytokine responses was due to the CD3+/CD30- T cell subset and not the CD3+/CD30+ subset, which predominantly produced both IL-10 and IFN-gamma, but only small amounts of IL-2 and IL-4. We conclude that immunodominant HCV core peptides induce preferentially type 1 cytokines in healthy anti-HCV-positive blood donors and CD30 expression in patients with chronic hepatitis C. However, in both groups, CD30+ T lymphocytes produce an intermediate Th0-like cytokine profile. Thus, chronicity in HCV infection may reflect a lack of type 1 cytokine production.