An increase in fibroblasts and associated connective tissue is a feature of pulmonary fibrosis. Activin A belongs to the transforming growth factor-beta (TGF-beta) supergene family and is known to have important roles in the induction of mesoderm and differentiation processes during development in early embryogenesis. It also modifies the growth and differentiation of various target cells. In this study we determined whether activin A could modulate human lung fibroblast (HFL1) activity, particularly with respect to proliferation and its differentiation into myofibroblast. A maximal effect on cell proliferation was observed at a low concentration of activin A (10(-11) M), and the effect of activin A was abolished by follistatin, an activin-binding protein. Activin A stimulated differentiation of HFL1 into myofibroblast in a dose-dependent manner. Thus activin A has potential effects on proliferation of lung fibroblast and its differentiation into myofibroblast, and may contribute to structural remodeling observed in pulmonary fibrosis.