Bacterial infection of the lower respiratory tract is initiated by colonization of the upper respiratory tract followed by aspiration of small volumes of contaminated secretions into the lungs. Failure of lung antibacterial defenses results in pneumonia. Strategies for prevention involve prevention of colonization, avoidance of aspiration, or enhancement of lung defenses. Effective prevention against specific organisms can be provided by immunization which enhances lung defenses for vaccinated strains. This approach has limited applicability because of the time required for development of protective antibody and the selective spectrum of protection. Aspiration of small quantities of oropharyngeal secretions is probably unavoidable in seriously ill patients. Prevention of colonization of the upper respiratory tract by pathogenic organisms would provide an effective prophylactic strategy. Although much has been learned about the role of bacterial adherence to regional epithelial cells in determining colonization, manipulation of this adherence phenomenon in the respiratory tract is not clinically possible at this time. The use of topical antimicrobial agents provides another means of preventing colonization with susceptible organisms. In human subjects and experimental animals, topical polymyxin B has successfully reduced cases of pneumonia due to Pseudomonas aeruginosa and Klebsiella pneumoniae, although colonization and occasional infections with resistant organisms occur. However, prevention of pneumonia by manipulation of the bacterial flora of the upper respiratory tract is an approach that warrants further investigation.