AIM: To evaluate, whether humoral hepatitis-B-vaccine non-responders also fail to mount a T cell response and to compare these results to normal vaccinees.METHODS: Fourty-seven health care employees were enrolled in this study including all available nonresponders (n = 13) with an anti-HBsAg titer 1000 kU/L as controls.PBMC from all subjects were analyzed by IFN-γ and IL-4 ELISPOT assays for the presence of hepatitis B surface antigen (HBsAg) reactive T cells.RESULTS: Non-responders and low-responders had no or only very limited T cell responses, respectively.Individuals responding to vaccination with the induction of a high anti-HBsAg titer showed a strong T cell response after the third vaccination.Surprisingly, these individuals showed response even before the first vaccination.T cell response to control antigens and mitogens was similar in all groups.CONCLUSION: Our data suggest that there is no general immune deficiency in non-/low-responders.Thus,we hypothesize that the induction of anti-HBsAg responses by vaccination is significantly dependent on the pre-existing T cell repertoire against the specific antigen rather than the presence of a general T cell defect.