Diastolic ventricular interaction is associated with septal shift and deformation, the consequences of which have not been fully assessed. A model was therefore developed to describe the mechanisms involved in interaction between the ventricles under different loading conditions. We assumed a circular cardiac minor-axis geometry surrounded by a pericardial membrane with the left ventricle (LV) and septum described by three layers. To define the equilibrium condition, we required the net force-balance at the right ventricular (RV)-LV intersection points to equal zero. The model was tested with and without consideration of bending forces associated with a change of curvature of a thick-walled structure. Model results were compared with data from animal experiments subjected to aortic and pulmonary constriction. LV and RV end-diastolic pressures as well as pericardial pressure were measured. In six dogs, septal segment length was measured using sonomicrometry, and in seven dogs, endocardial curvature was measured using echocardiography. Model and experimental results show that 1) with severe RV loading, septal inversion occurs at a negative transseptal gradient, and 2) the end-diastolic septal segment length continues to shorten after septal inversion during pulmonary constriction. Model simulation suggests that bending moments account for the septal curvature at zero transseptal pressure. In addition, the model predicts the shift in the pressure-area relationship of each ventricle by a change in loading of the opposite ventricle and predicts that large transmural gradients in stress and strain are associated with septal inversion. Thus the model and the experimental data agree and describe the important factors that modulate diastolic septal mechanics during acute differential ventricular loading.