Interleukin (IL)-17F is a recently described human cytokine belonging to the IL-17 gene family, but its in vivo function remains to be determined. To this end, a full-length mouse IL-17F cDNA sequence with a 483-bp coding region sequence was first identified. Pulmonary gene transfer of an IL-17F expression construct (pcDNAmIL-17F) in mice was used to investigate its regulatory role. The results showed first that a significant increase in the number of neutrophils was seen in the bronchoalveolar lavage fluids of IL-17F-transduced mice, concomitant with increased expression of genes encoding C-X-C chemokines and inflammatory cytokines when compared with mock and phosphate-buffered saline control animals. Mucosal transfer of the IL-17F gene in ovalbumin (OVA)-sensitized mice before antigen (Ag) challenge enhanced the levels of Ag-induced pulmonary neutrophilia, but not eosinophilia, goblet cell hyperplasia, and mucin gene expression. However, no significant change in the levels of Th2 cytokine expression was noted. A significant enhancement of ventilatory timing in response to inhaled methacholine was also seen in IL-17F-transduced, Ag-sensitized mice, whereas a small but significant increase was found in IL-17F-transduced, naive mice. These results suggest a role for IL-17F in the induction of neutrophilia in the lungs and in the exacerbation of Ag-induced pulmonary inflammation.