Cardiomegaly results from the growth of muscle fibers, coronary vessels, connective tissue and other constituents of the myocardial wall. An attempt has been made to explain the growth of these tissues by a unifying concept, namely, a sustained increase in stroke energy expenditure per unit mass of myocardium. Myocardial growth seems to be initiated by the earliest biochemical change, namely, the increased production and utilization of energy-rich phosphates which are essential for protein synthesis. Coronary growth is considered to be the result of increased tangential stress in the vascular wall as a consequence of vasodilatation due to increased metabolites from the myocardium and decreased PΘ2 in myocardial tissue fluids. Acceleration of the biosynthesis of collagenous protein is believed to be the result of decreased Po2 in the interstitial fluids of the myocardium as a consequence of increased oxygen consumption of contractile elements. According to this concept, increased aerobic energy production of the myocardium per beat per unit mass of tissue plays a key role in the development of cardiomegaly.