Expression of CD11b is enhanced on neutrophils recruited to the lungs during bacterial pneumonia. To determine the role that CD11b plays in pneumonia, CD11b gene-deficient (CD11b(-/-)) mice and normal wild-type (wt) mice were intranasally infected with Streptococcus pneumoniae. CD11b(-/-) mice had an enhanced outgrowth of pneumococci in the lungs and an increased dissemination of the infection, which could be reproduced by treatment of wt mice with an anti-CD11b antibody. This reduced resistance was associated with higher neutrophil counts in bronchoalveolar lavage fluid and lung tissue and an exaggerated lung inflammatory response. CD11b is important for an effective defense against S. pneumoniae pneumonia but not for recruitment of neutrophils.