In mammals, interleukin-21 (IL-21) is an immunomodulatory cytokine with pleiotropic effects on the proliferation, differentiation and effector functions of T, B, NK and dendritic cells. A cDNA encoding the chicken orthologue of IL-21 (chIL-21) was cloned by RT-PCR from RNA isolated from activated chicken splenocytes and consists of 438 nucleotides, encoding an open reading frame of 145 amino acids (aa). Chicken IL-21 has 20-30% aa identity to its orthologues in mammals, Xenopus and fish, but is more highly conserved within Aves (50-80%). The four alpha-helical bundle structure of mammalian IL-21 appears to be conserved in the predicted chicken protein, as are the four cysteine residues required for the formation of two disulphide bridges. A glutamine residue in aa position 129, which has been implicated in the binding of IL-21 to the IL-2 receptor γ-chain in mammals, is also conserved. ChIL-21 is expressed in most lymphoid tissues, predominantly by CD4+ TCRαβ+ T cells. As in mammals, chIL-21 synergistically enhances T-cell proliferation and inhibits maturation of dendritic cells.