Splenosis has been shown to occur after traumatic injury to the spleen. It is postulated that this is the mechanism for the low incidence of bacterial infection in this group of patients when compared to those who undergo splenectomy for other reasons. Therefore, we studied the effect of exposure to an aerosolized suspension of type III Streptococcus pneumoniae on splenectomized mice who had either all or half of their splenic tissue cut up and reimplanted into the abdominal cavity 8 wk prior to bacterial exposure. It was determined that the mortality experience of these two groups of mice was similar to each other and no different from the sham control group, although all three groups had a statistically significant lower mortality experience than the splenectomized control group. This study demonstrates that splenosis in mice can protect against aerosolized bacterial infection.