Overstretching the intact ventricle increases global compliance as a function of maximum previously experienced load and may have an important role in the diseased heart, but the corresponding changes in local myocardial mechanics and structure are unknown. Therefore, we measured two-dimensional strain on the left ventricular (LV) epicardium in isolated arrested rat hearts sequentially inflated to increasing cavity pressures of 10, 30, and 120 mmHg. Strains at matched LV pressures increased significantly (P < 0.002) as the maximum pressure previously experienced by the LV (Pmax) increased. Compared with Pmax = 10 mmHg, relative increases in fiber strain for Pmax = 30 and 120 mmHg (100 and 149%, respectively) were significantly greater (P < 0.001) than the corresponding increases in cross-fiber (51 and 78%, respectively) and fiber shear (57 and 86%, respectively) strains. Using an optimized prolate spheroidal finite-element model of the rat LV that reliably reproduced experimental strains, we estimated progressive decreases in epicardial biaxial wall stiffness up to 87% with increasing Pmax that were not different in the fiber and cross-fiber directions. Thus, although passive ventricular overloading causes direction-dependent increases in epicardial strain, these changes are the consequence of local myocardial softening that is actually independent of direction.