['Added transforming growth factor beta (TGFbeta) inhibits the proliferation of immature cardiomyocytes. We have now examined the hypothesis that suppression of endogenous TGFbeta signaling will boost the proliferative response (DNA synthesis) of cardiac myocytes to serum and/or to the mitogenic factor fibroblast growth factor-2 (FGF-2).', 'Overexpression of a kinase-deficient TGFbeta type II receptor (TGFbetaRIIDeltaKD) resulted in a 2.8-fold increase in cardiomyocyte DNA synthesis in serum-rich cultures, an effect requiring active FGFR-1 since it was not observed in the presence of excess kinase-deficient FGFR-1. This finding suggested that endogenous TGFbeta-TGFbetaRII suppressed endogenous FGFR-1-mediated signals that stimulate or are permissive for DNA synthesis. TGFbeta had no effect, however, on the FGF-2-induced acute stimulation of extracellular signal regulated kinase1/2. FGF-2, added in the absence or presence of TGFbeta inhibition, elicited a 3- or a 13-fold stimulation of DNA synthesis, respectively, pointing to a synergistic effect.'] Does inhibition of TGFbeta signaling potentiate the FGF-2-induced stimulation of cardiomyocyte DNA synthesis?