Activins are potentially important regulators of early developmental processes in vertebrates. Although the different forms of activin appear to be differentially expressed during early amphibian, avian, and murine development, little is known about the factors that regulate their expression. In this study we report the qualitative effects of several growth and differentiation factors on the expression of inhibin subunits in three differentiated cell lines derived from P19 embryonal carcinoma cells. These cell lines include mesodermal (MES-1), neuroepithelial (EPI-7), and visceral endoderm-like (END-2) cell types, expressing both inhibin beta A and beta B subunit mRNAs. We have shown for the first time that this expression is modulated by transforming growth factor (TGF)beta 1 and TGF beta 2 but not significantly by other growth factors such as leukemia inhibitory factor or members of the fibroblast growth factor family (aFGF, bFGF, or kFGF). beta A mRNA expression is increased while beta B expression is simultaneously decreased by TGF beta. Furthermore, TGF beta increased the amount of bioactive activin secreted by MES-1 and END-2 cells. Inhibin alpha subunit mRNA expression is not affected by TGF beta. These results point to a possible role of type beta transforming growth factors as regulators of activin expression in embryonal cells.