Transforming growth factor beta (TGF-beta) signaling plays an important role in the pathogenesis of cardiac hypertrophy. However, the molecular mechanism of TGF-beta signaling during the process of cardiac remodeling remains poorly understood. In the present study, by employing single-molecule fluorescence imaging approach, we demonstrated that in neonatal rat cardiomyocytes. TGF-beta type II receptors (T beta RII) existed as monomers at the low expression level, and dimerized upon TGF-beta 1 stimulation. Importantly, for the first time, we found the increased dimerization of T beta RII in hypertrophic cardiomyocytes comparing to the normal cardiomyocytes. The enhanced T beta RII dimerization was correlated with the enhanced Smad3 phosphorylation levels. These results provide new information on the mechanism of TGF-beta signaling in cardiac remodeling. (C) 2011 Elsevier Inc. All rights reserved.