Polymorphonuclear leukocytes (PMN) play an important functional role in early pulmonary clearance of Streptococcus pneumoniae. The factors responsible for PMN recruitment to the lung after challenges with this organism are poorly defined. We used congenic C5-sufficient B10.D2/nSn (C5+) and C5-deficient B10.D2/oSn (C5-) mice to determine the importance of the C5 molecule in the PMN response to S. pneumoniae. The C5+ and C5- mice were injected with water and varying inoculums of pneumococci via an endobronchial catheter. Bronchoalveolar lavage (BAL) was performed on the inoculated lung at 0 and at 4 h after injection. Cellular response was measured and chemotactic activity was assayed in BAL supernatants at each time interval using human PMN in modified Boyden chambers by the leading front technique. Clearance of bacteria was studied by quantitative lung culture. The C5+ mice recruited significantly more PMN after challenges with both 10(4) and 10(6) pneumococci than did the C5- mice (p less than 0.05), but significant PMN accumulation did occur in C5- mice. Similarly, C5+ mice generated significantly more intraalveolar chemotactic activity than did C5- mice (p less than 0.05) but chemotactic activity was present in both C5+ and C5- mice in checkerboard assays. Pulmonary clearance of bacteria was significantly impaired in the absence of C5 at both inoculums (p less than 0.05). Our results indicate that the C5 molecule yields important PMN chemotaxins during the early time period after intrapulmonary inoculation of S. pneumoniae. However, PMN recruitment after this insult also results from other chemotaxins because both chemotactic activity and PMN recruitment occur within the alveoli of C5- mice.