Activin A, a member of the transforming growth factor-beta superfamily, is released rapidly into the circulation during inflammation. This review examines the evidence that activin is a critical mediator of inflammation and immunity. Activin modulates several aspects of the inflammatory response, including release of pro-inflammatory cytokines, nitric oxide production and immune cell activity. Crucially, inhibiting activin with follistatin, a high affinity binding protein, alters the pattern of cytokines released and improves survival in a mouse model of endotoxic shock. Serum and tissue concentrations of activin are elevated in a wide range of pathological conditions. The utility of activin as a diagnostic marker of clinical inflammation and the use of follistatin to block activin actions therapeutically are also discussed.