Rationale: TGF- has a central role in driving many of the pathological processes that characterize pulmonary fibrosis. Inhibition of the integrin v6, a key activator of TGF- in lung, is an attractive therapeutic strategy, as it may be possible to inhibit TGF- at sites of v6 upregulation without affecting other homeostatic roles of TGF-. Objectives: To analyze the expression of v6 in human pulmonary fibrosis, and to functionally test the efficacy of therapeutic inhibition of v6-mediated TGF- activation in murine bleomycin-induced pulmonary fibrosis. Methods: Lung biopsies from patients with a diagnosis of systemic sclerosis or idiopathic pulmonary fibrosis (IPF) were stained for v6 expression. A range of concentrations of a monoclonal antibody that blocks v6-mediated TGF- activation was evaluated in murine bleomycin-induced lung fibrosis. Results: v6 is overexpressed in human lung fibrosis within pneumocytes lining the alveolar ducts and alveoli. In the bleomycin model, v6 antibody was effective in blocking pulmonary fibrosis. At high doses, there was increased expression of markers of inflammation and macrophage activation, consistent with the effects of TGF- inhibition in the lung. Low doses of antibody attenuated collagen expression without increasing alveolar inflammatory cell populations or macrophage activation markers. Conclusions: Partial inhibition of TGF- using v6 integrin antibodies is effective in blocking murine pulmonary fibrosis without exacerbating inflammation. In addition, the elevated expression of av6, an activator of the fibrogenic cytokine, TGF-, in human pulmonary fibrosis suggests that v6 monoclonal antibodies could represent a promising new therapeutic strategy for treating pulmonary fibrosis.