In search for a parameter that is predictive of long-term immunity, we analysed the influence of booster immunisations on frequencies of circulating memory B-lymphocytes. Specific IgG-secreting B-cells were determined by ELISPOTassay in 13 healthy adults, using diphtheria and tetanus toxoid as model antigens. Our results show that memory B-cells accumulate with every immunisation dose and remain elevated over several years. In addition, secondary B-cell responses were studied during the first 90 days after diphtheria re-immunisation. A significant indirect correlation was found between the number of previous boosters and the magnitude of specific B-cell expansion. In contrast, effects of booster immunisations did not correlate likewise with antigen-specific serology. Hence, this study illustrates that frequencies of antigen-specific B-lymphocytes can be used as an indirect measure for immunological memory. This parameter could be helpful to find scientifically based immunisation strategies for currently available and novel vaccines.