In heart failure, many alterations occur in the ventricle as a whole, as well as in the myocardial cell. In the first part of this review we report on the macroscopic structure of the left ventricle by analysing the relation between left ventricular dilatation and left ventricular hypertrophy in terms of ventricular wall stress. Peak systolic stress in dilated ventricles of patients with compensated heart failure does not differ from values obtained in normal ventricles, whereas the systolic stress-time integral is increased by more than 40%. The stress-time integral is a major determinant of myocardial oxygen consumption, and its reduction by peripheral vasodilation leads to a proportional decrease in left ventricular oxygen consumption. In contrast, the phosphodiesterase inhibitor, enoximone, decreases the stress-time integral without a proportional decrease in myocardial oxygen consumption, due to the competition between positive inotropic effect with increased oxygen consumption and a vasodilating effect with decreased oxygen consumption. Beta-1 adrenoceptor agonists increase myocardial oxygen consumption. In the second part of this review we report on the functional alterations of the following subcellular and molecular structures in the failing myocardium: (1) adrenoceptors and G-proteins; (2) sarcoplasmic reticulum with an altered force-frequency relationship; (3) the acto-myosin system with decreased velocity of shortening and increased economy of force generation. On the basis of these alterations, a disadvantageous chain of events develops in the failing myocardial cell.