To determine the effects of aging on the human myocardium, 67 hearts were obtained from individuals who died from causes other than cardiovascular disease. The age interval examined was 17-90 years. Regression analysis demonstrated that the aging process was characterized by a loss of 38 million and 14 million myocyte nuclei/yr in the left and right ventricular myocardium, respectively. This loss in muscle mass was accompanied by a progressive increase in myocyte cell volume per nucleus in both ventricles. Left ventricular myocytes enlarged by 110 microns3/yr, whereas right ventricular myocytes increased by 118 microns3/yr, resulting in a preservation of ventricular wall thickness. However, the cellular hypertrophic response was unable to maintain normal cardiac mass. Left and right ventricular weights decreased by 0.70 and 0.21 g/yr, respectively. In conclusion, loss of cells and enlargement of the remaining myocytes may represent the structural basis for the reduced compensatory capacity of the aged heart and together may contribute to the development of myocardial dysfunction and failure in the elderly.