In all of the IL-13 transgenic mice, IL-13 induced an eosinophil-rich, macrophage-rich, and lymphocyte-rich pulmonary inflammatory response. To obtain insight into the mechanisms that might be responsible for this response, studies were undertaken to determine whether IL-13 induced C-C chemokines in these animals. Reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, in situ hybridization, and/or Northern blot evaluations demonstrated that IL-13 is a powerful inducer of eotaxin-1, eotaxin-2, monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, MCP-5, macrophage inflammatory protein (MIP)-1α, MIP-1β, C10, monocyte-derived chemokine, thymus and activation-regulated chemokine, thymus-expressed chemokine, MIP-3, and KC. The levels of induction of MCP-1, eotaxin-1, and C10 were particularly powerful. Because of the large number of chemokines that were induced by IL-13, studies were next undertaken to determine whether any of these inductive events played a key role in the generation of the IL-13-induced phenotype. The interaction of MCP-1 and its receptor, chemokine receptor (CCR) 2, was chosen for these studies because MCP-1 was one of the earliest chemokines that was induced by IL-13. In these studies, IL-13 transgenic mice were bred with mice with wild-type (+/+) or null mutant (−/−) CCR2 loci, and the effects of IL-13 in the presence and absence of CCR2 were compared. These studies demonstrated that CCR2 signaling plays a critical role in the generation the IL-13-induced phenotype because transgenic mice that were deficient in CCR2 had markedly diminished tissue inflammation, decreased BAL cellularity (without a change in the BAL cell differential), decreased lung size, decreased pulmonary compliance, decreased alveolar size, and diminished subepithelial collagen accumulation. The latter were due, at least in part, to the decreased ability of IL-13 to stimulate the production of transforming growth factor (TGF)-β1 in this setting (see below).