Although antisense strategy has been at the center of interest in gene therapy, little is known about application of this strategy to cardiac diseases because of the lack of a suitable delivery method into the heart. Therefore, we compared the transfection efficiency of antisense oligodeoxynucleotides (ODN) using HVJ-liposome method and direct transfer in in vivo transfer into heart. To investigate the cellular fate and localization of ODN, transfer of "naked" FITC-labeled antisense ODN or ODN enwrapped in HVJ-liposome complex were examined. Following in vivo transfer using direct injection as well as in vitro transfer, fluorescence rapidly disappeared within 1 day, whereas transfer by HVJ-liposome method resulted in sustained fluorescence localized in the nucleus for at least 1 week. Measurement of fluorescence also demonstrated a significantly higher level in myocardium transfected by HVJ-liposome method than direct transfer. The present study demonstrated that HVJ-liposome method is more efficacious for ODN delivery by prolongation of half-life of ODN, suggesting its usefulness for gene therapy in cardiac diseases.