Inducible heat shock protein 70 (HSP70) is an intracellular stress protein that confers cytoprotection to a variety of cellular stressors. Recent reports have established that the overexpression of HSP70 mammalian cell lines confers protection against several noxious stresses like hyperthermia, hypertonic stress, and various cytotoxic agents, including cytoskeletal disruptors. Several lines of evidence have suggested that augmentation of the heat shock response by increasing the expression of HSP70 represents a potential therapeutic strategy for the treatment of critically ill patients. In this study, we used a novel approach to study the potential cytoprotective effect of HSP70 as a therapeutic agent in rat myogenic cell line H9c2 and primary neonatal cardiomyocytes. In the current study, we cloned a human HSP70 cDNA gene and fused it with a gene fragment encoding the 11-amino acid transduction domain of HIV-1 TAT protein. We then analyzed the efficiency of transduction of the resulting TAT-HSP70 fusion protein into rat myogenic cell line H9c2. Finally we determined the ability of TAT-mediated transduction of the HSP70 protein to confer cytoprotection against a serum starvation and hypoxic insult. The experimental data we reported here suggest that the TAT-mediated delivery of HSP70 may represent a novel strategy of augmenting intracellular HSP70 levels. [This study was supported by a grant of the Student Research Funds in 2003, Yonsei University College of Medicine.]