We investigated whether strain softening (or the Mullins effect) may explain the reduced left ventricular stiffness previously associated with the strain-history-dependent preconditioning phenomenon. Passive pressure-volume relations were measured in the isolated, arrested rat heart during LV balloon inflation and deflation cycles. With inflation to a new higher maximum pressure, the pressure-volume relation became less stiff, particularly in the low (diastolic) pressure range, without a significant change in unloaded ventricular volume. In five different loading protocols in which the maximum passive cycle pressure ranged from 10 to 120 mmHg, we measured increases at 10 mmHg in LV volume up to 350 percent of unloaded volume that depended significantly on the history (p < 0.05) and magnitude (p < 0.01) of maximum previous pressure. Although a quasi-linear viscoelastic model based on the pressure-relaxation response could produce a nonlinear pressure-volume relation with hysteresis, it was unable to show any significant change in ventricular stiffness with new maximum pressure. We incorporated a strain softening theory proposed by Johnson and Beatty (1992) into the model by modifying the elastic response with a volume-amplification factor that depended on the maximum previous pressure. This model more accurately reproduced the experimentally observed behavior. Thus, the preconditioning behavior of the myocardium is better explained by strain softening rather than viscoelasticity and may be due to damage to elastic components, rather than the effect of viscous tissue components.