CHF is, by definition, due to a defect rather than an excess of function. Therefore, it may be accessible to targeted delivery of a cDNA encoding a protein whose decreased expression directly participates in the reduced contractility of the failing heart. Gene transfer to the myocardium must address several specific issues, in addition to those applying to gene therapy in general: (i) the potential targets; (ii) how to reach these targets in vitro? (iii) does gene transfer restore the compromised function in vitro? (iv) how to deliver genes to the cardiac myocyte in vitro? and (v) does gene transfer restore the compromised function in vivo? Current data indicate that cardiac myocytes are good recipient cells for gene delivery in vitro, and that in vivo, intracoronary delivery systems might permit recombinant gene expression to be localized to the appropriate cardiac cells. There is no reason to believe that diseases of the myocardium will remain outside the scope of gene therapy...