Objective: The aim of this study was to evaluate the response to hepatitis B vaccination in isolated anti-HBc positive subjects. Patients and Methods: Forty-eight subjects with persistent isolated core antibody were included in the study. Fifty healthy people who were negative for HBsAg, anti-HBs and anti-HBc were included in the study as a control group. They all were vaccinated with recombinant hepatitis B vaccine at 0, 1 and 2 months. Results: Thirty days after each dose of vaccination, serum levels over 10 IU/l of anti-HBs are found in 50% of the subjects with isolated anti-HBc after first; in 68.7% after second and in 89.6% after third vaccination. There were no statistical differences between the two groups (P > 0.05). Twenty subjects in isolated anti-HBc group (41.6%) but none of the subjects from the control group responded with a titer of > 50 IU/l after 30 days, which suggested an anamnestic response due to prior infection and immunity. Furthermore, 23 subjects in isolated anti-HBc group (47.9%) finally responded after three doses of vaccination (anti-HBs titer > 10 IU/l) thus excluding chronic infection and suggesting initial false positive results. Conclusions: In isolated anti-HBc subjects false positive results (primary response) or prior infection by HBV (anamnestic response) can be detected by anti-HBs response after HBV vaccination. © 2001 The British Infection Society.