Background.We have demonstrated that cyclosporine (CsA) stimulates transforming growth factor (TGF) β1expression in vitro and that growth of mammalian cells can be arrested by CsA via a TGF-β1-dependent mechanism. Herein, we have explored whether CsA stimulates TGF-β1hyperexpression in vivo.Methods.Four groups of B6AF1 mice were studied: group 1, control; group 2, CsA pretreatment; group 3, anti-CD3 monoclonal antibody pretreatment; and group 4, CsA plus anti-CD3 pretreatment.Results.CsA pretreatment augmented TGF-β1protein expression and increased intrarenal display of TGF-β1mRNA. This heightened TGF-β1expression was associated with an impaired T cell proliferative response.Conclusions.Our observations, together, advance the hypothesis that CsA might function in vivo as an immunosuppressant not only by inhibiting the expression of proinflammatory cytokines (e.g., interleukin 2), but also by stimulating the expression of TGF-β1, a potent immunosuppressive cytokine. Moreover, prevention of TGF-β1hyperexpression might prevent CsA-associated renal fibrosis, as TGF-β1is a fibrogenic cytokine.