The effect of activins A, AB, and B on hepatocyte growth factor (HGF) synthesis stimulated by 12-O-tetradecanoylphorbol beta-acetate (TPA) was studied in MRC-5 human lung fibroblasts. Activins A, AB, and B inhibited the increase in HGF secretion induced by TPA in different dose-dependent manners and potencies. At 5 ng/ml, activins A and AB inhibited the increase approximately 30% and 10%, respectively, and at 25 ng/ml both activins produced almost maximal inhibition, i.e., approximately 40%. Activin B caused 10% inhibition at 12 ng/ml, and at 25 ng/ml produced almost maximal inhibition, approximately 30%. Further analysis with activin A indicated that the inhibition was caused by decreased HGF mRNA levels, followed by decreased cellular HGF levels. At 25 ng/ml, activin A inhibited the increase in HGF in the cellular lysate and the increase in HGF mRNA level approximately 80% and 40%, respectively.