This study evaluated the immunogenic and protective effects of plasma-derived and DNA recombinant anti-hepatitis B virus vaccines administered to infants at various ages and with different vaccination schedules: 3 monthly doses in the first 3 months of life, 3 doses (at 3, 5 and 11 months) or 2 doses (at 1 and 3 months) or 2 doses (at 3 and 5 months). Anti-HBs (hepatitis B surface) and anti-HBc (hepatitis B core) markers were investigated twice: one month and ten years after vaccination in 261 children immunized with plasma-derived vaccine, and one month and five years after vaccination in 449 children immunized with DNA recombinant vaccine. In all groups, the appearance of anti-HBs protective levels one month after vaccination and their persistence in the following years were found in a larger number of subjects when the vaccine doses had been administered after the third month of life rather than in the first three months. Moreover, our results show that the reappearance of surface antibodies a week after the booster, in vaccinated children who became anti-HBs- in the years following vaccination, occurred in a larger number of subjects when the primary vaccination with 3 doses had been performed in the first quarter or with 2 or 3 doses in the second quarter. In contrast, protective levels of anti-HBs were found in a small number of children belonging to the group vaccinated with 2 doses in the first three months, and among them the majority seroconverted only one month after the booster. Anti-HBc was found 10 years after vaccination in only one child immunized with 2 doses of plasma-derived vaccine, and 5 years after vaccination in two children immunized with 2 doses of DNA recombinant vaccine. All these children were found to lose anti-HBs, and none of them had signs of disease or became a carrier. Based on these results, the disappearance, in some children, of protective levels of anti-HBs in the years following vaccination does not mean the loss of anti-HBV protection. In fact, the trial showed that they reacted immediately to booster stimulation, demonstrating a solid immunologic memory. Therefore, there may be no reason for giving booster injections when the vaccination of infants is carried out correctly.