We developed a mathematical model of the right and left ventricles to determine whether there is a change in the mechanical properties of muscle during the hypertrophy process resulting from pulmonary arterial banding. Pressure-volume data were obtained from 10 normal dog hearts and 8 dog hearts in which the pulmonary artery was banded for periods of 2-40 weeks. These data were applied to the model, and the time course of wall stress and muscle stiffness was quantified for both ventricles. The results demonstrate that (1) myocardial stiffness is increased in pressure-overload hypertrophy (2) normal right and left ventricular muscle exhibits similar mechanical properties and(3) the relationships between wall stresses and the volume/mass ratios to the period of banding are biphasic. We concluded that (1) increase in muscle stiffness is due to several factors. In the early stages of hypertrophy, it may be predominantly due to fibrosis and, in the later stages, to substantial increases in muscle mass. (2) The progressive increase in muscle stiffness concomitant with the increase in muscle mass may be due to the presence of myocardial cellular projections and fibrosis. (3) The appropriate timing for surgical/medical intervention should take place before low volume: mass ratios and, hence, low wall stresses are attained. Circ Res 46: 530-542, 1980