Long-term hepatitis B reinfection prophylaxis after liver transplantation with hepatitis B immunoglobulin (HBIG) and nucleoside analogues is expensive and inconvenient. Studies evaluating humoral immune responses to hepatitis B virus (HBV) vaccines showed conflicting results. Best results were achieved under continuous HBIG administration with an adjuvant-containing HBsAg vaccine. In the present study, 8 patients who had been HBsAg positive and HBV DNA negative prior to liver transplantation were immunized with HBsAg-vaccine containing the adjuvant 3-deacylated monophosphoryl-lipid-A. Vaccination was started after discontinuation of HBIG. Six vaccinations were administered at weeks 0, 2, 4, 12, 16 and 24. Humoral (anti-HBs titres) and cellular (enzyme-linked immunospot assay and fluorescence-activated cell sorting analysis) immune responses were studied. Only one of eight patients responded with a humoral immune response (maximum anti-HBs titre 561 U/l). In this patient, decrease of anti-HBs titre before vaccination was significantly slower than in the other seven patients and anti-HBs did not become negative before first vaccination. A T-cell response to HBsAg could not be detected in any of the patients. The responder was the only patient who showed a T-cell response to HBcAg. In conclusion, the adjuvant-containing vaccine did not induce a humoral or a detectable cellular immune response in most patients. Patient-related preconditions and concomitant HBIG administration should be further investigated as possible predictors for response.