Splenectomized individuals are at increased risk of acquiring fulminant pneumococcal infections. In an experimental mouse model, we have studied how removal of the spleen influences the anti-pneumococcal antibody response to s.c. primary immunization with a 23-valent pneumococcal polysaccharide vaccine and to re-immunization 5 months later. In splenectomized BALB/c mice the antibody response to serotypes 1, 4, 7F, and 19F was reduced both after the first and after the second immunization, compared to that in normal mice. In contrast, splenectomized and normal CBA/J mice produced similar antibody levels to serotypes 1 and 4 after the second immunization, although the response to these serotypes was reduced in splenectomized mice after the first immunization. After i.v. injection with heat-killed pneumococci serotype 4, splenectomized BALB/c mice that had been immunized 5 months earlier with 23-valent vaccine were able to mount higher antibody levels which were reached earlier than in unprimed splenectomized mice. However, normal mice that had been vaccinated 5 months earlier had the highest antibody levels after immunization with pneumococci. Our results indicate that although splenectomized mice generally do not reach as high antibody levels as are seen in normal mice after pneumococcal immunization, they benefit from previous immunization with regard to antibody levels when given a second antigen challenge.