Transforming growth factor beta (TGF-beta) is a pleiotropic cytokine with important roles in the regulation of cell proliferation, differentiation, survival, migration, activation and deactivation. It is one of the first cytokines released during an immune response and plays a strong immunomodulatory role in the activation and subsequent de-activation of macrophages and other immune cells. TGF-beta is a highly conserved molecule, and members of the TGF superfamily can be found in organisms as evolutionarily distant as arthropods. In this manuscript, we described the identification of a goldfish TGF-beta molecule, which was highly expressed in the skin, kidney and spleen of the goldfish and its expression was up-regulated in macrophages treated with LPS or recombinant goldfish TNF-alpha. Goldfish TGF-beta shared a high amino acid identity with, and was phylogenetically related to, TGF-beta 1 of other teleost fish, birds, amphibians and mammals. Recombinant goldfish TGF-beta (rTGF-beta) induced the protiferation of a goldfish fibroblast cell line (CCL71) in a dose-dependent manner. In addition, rTGF-beta down-regulated the nitric oxide response of TNIF-alpha-activated macrophages. This is the first report of teleost TGF-beta function in an ectothermic vertebrate. (C) 2007 Elsevier Ltd. All rights reserved.