Interleukin-17 (IL-17) is a proinflammatory cytokine produced by activated T cells. A 917-bp cDNA encoding the IL-17 gene was isolated from our EST cDNA library prepared from intestinal intraepithelial lymphocytes (IELs) of Eimeria-infected chickens. It contained a 507-bp open reading frame (ORF) predicted to encode a protein of 169 amino acids (aa) with a molecular mass of 18.9 kDa, a 27-residue NH(2)-terminal signal peptide, a single potential N-linked glycosylation site, and 6 cysteine residues conserved with mammalian IL-17. Chicken IL-17 (chIL-17) shared 37%-46% amino acid sequence identity to the previously described mammalian homologs and also was homologous to the ORF 13 of Herpesvirus saimiri (HVS 13). By Northern blot analysis, IL-17 transcripts were identified in a reticuloendotheliosis virus (REV)-transformed chicken lymphoblast cell line (CU205) and conconavalin A (ConA)-stimulated splenic lymphocytes but not other chicken cell lines or normal tissues. Conditioned medium from COS-7 cells transfected with ChIL-17 cDNA induced IL-6 production by chicken embryonic fibroblasts, suggesting a functional role for the cytokine in avian immunity.