The inability of cardiac muscle cells to replicate in adult myocardium con founds recovery from ischemic injury and contrasts with the excessive growth of vascular smooth muscle in atherosclerotic lesions. Growth of cardiac myocytes by cell enlargement, however, is one outcome of pressure and volume overload, which encompasses not only inc eased RNA; protein, cell volume and mass, but also plasticity of gene expression. Consequently, cardiac hypertrophy presents a challenging phenomenon to molecular geneti cists, to explicate transducing mechanisms that couple mechanical load to long-term changes in cardiac function and structure. Recent advances toward understanding trophic signals in the heart and remaining enigmas constitute the subject of this review. An ensemble of cardiac gene products exists, more extensive than recognized previously, which is coordinately regulated during experimental hypertrophy and myocar dial disease. Whether such genetic responses signify a purely adaptive re sponse or, instead, a shared regulatory program is controversial. Molecular signals that might initiate growth and alter gene expression after hemodynam ic stress have been identified. Induction of nuclear oncogenes during cardiac