The efficacy of pneumococcal vaccine given after splenectomy lacks experimental validation. Adult CD-1 male mice that received type III pneumococcal capsular polysaccharide vaccine 1 microgram IP, 48 hours postsplenectomy and 7 days before challenge with aerosolized type III Streptococcus pneumoniae had a significantly higher mortality (96%) compared to immunized controls (64%) (p less than 0.002). The vaccine protected immunized sham-operated mice compared to unimmunized controls (p less than 0.015). Mice immunized 7 days before splenectomy were equally protected when compared to immunized sham-operated mice (p = NS). All deaths were secondary to culture-proven pneumococcal infection. These findings corroborate previous experimental and clinical studies demonstrating an impaired immunologic response and increased susceptibility to infection in asplenic individuals. Pneumococcal vaccines should be given before nonemergent splenectomy. Alternatives to splenectomy should be considered for patients with traumatized spleens where possible.