The benefit of re-immunization with pneumococcal polysaccharide vaccine is an important question in clinical practice. In an experimental model, BALB/c and CBA/J mice were re-immunized s.c. with a 23-valent pneumococcal polysaccharide vaccine at various time intervals after a first immunization with the same vaccine. The antibody response after the secondary immunization showed similar kinetics as after primary immunization, and was mainly an IgM antibody response. Re-immunization at 28 days or earlier induced a decrease in the serum antibody levels to the vaccine. Reimmunization at 120 days or later induced higher antibody levels than after the first immunization. Significant increases in antibody levels to serotypes 1, 4, 7F and 19F out of six serotypes tested were observed. In CBA/J mice, but not in BALB/c mice, the dose used for primary immunization appeared to influence the magnitude of the antibody response to secondary immunization. Our results indicate that the time interval between primary and secondary immunization is an important determinant with regard to the magnitude of the antibody response to re-immunization with pneumococcal polysaccharide vaccine.