In the prior two reports, we demonstrated that G-CSF induced the polarization of neutrophils by itself, and also enhanced superoxide production from neutrophils stimulated by the chemotactic peptides. In this study, we have examined the protective effect of G-CSF in vivo on Pseudomonas pneumonia and septicemia in mice. Cyclophosphamide (CY) induced severe reduction of the number of peripheral leukocytes and weakened resistance for Psuedomonas aeruguinosa infection of mice. However, in mice receiving recombinant human G-CSF four daily subcutaneous injection, the number of leukocytes, particulary neutrophils, increased more rapidly than in controls receiving saline. Moreover G-CSF enhanced a protective effect to pulmonary and systemic pseudomonas infections. When G-CSF was administered together with antibiotics, significant synergism in the protection against pulmonary infection of Pseudomonas was observed. Carrageenan treatment decreased the protective effect of G-CSF. These results suggested that the protective effect of G-CSF against P. aeruginosa infection depends not only on PMN but also another complexed host defence mechanism.