We assessed in a western population the efficacy of a plasma-derived hepatitis B vaccine in relatives of highly infectious hepatitis B virus (HBV) carriers. A consecutive group of 103 HbsAg, anti-HBs and anti-HBc negative household relatives of 45 HBV-DNA positive chronic carriers received a 5 micrograms dose of plasma-derived vaccine at 0, 1, 2 and 12 months. Protective levels of immunity developed in 101 subjects (97.8%) 3 months after boosting. Low responders to the vaccine were mostly found among parents and spouses of carriers, whilst offspring and siblings were usually high responders. The main discriminant in predicting a good response was age below 12 years. Hyporesponsiveness did not occur in family clusters. No major HBV events occurred among immunized relatives patients. Hepatitis B vaccine is safe and effective in immunizing relatives of HBV carriers while no genetic conditioning of the immune response is evident among them.