Despite the fact that myofibers would be expected to shorten only along their axes, there is now evidence for substantial deformation away from the local myofiber direction in the left ventricle. To determine if the principal directions of deformation could be altered by a physiological stimulus, we examined local three-dimensional finite deformation in the anterior free wall of the left ventricle during normal atrial activation (AA) and, subsequently, during epicardial ventricular pacing (VP) at the site of deformation measurement in open-chest anesthetized dogs. An analysis of variance by repeated measures revealed the following significant changes (P less than or equal to 0.05) in the overall (average of epicardial and endocardial data) strain variables at end systole. Circumferential strain increased from -0.07 (AA) to 0.14 (VP), radial strain decreased from 0.16 (AA) to 0.01 (VP), shear in the tangent plane of the local epicardium decreased from 0.04 (AA) to -0.02 (VP), shear in the plane of the longitudinal and radial coordinates decreased from 0.03 (AA) to -0.03 (VP). Neither the first (greatest shortening) nor the third (greatest lengthening) principal strain changed significantly, but the direction of the first principal axis of deformation projected on the epicardial tangent plane changed from -51 degrees (AA) to -80 degrees (VP) from circumferential. In addition, substantial tipping of the plane of principal shortening away from the epicardial tangent plane was observed, particularly with ventricular pacing. These data indicate that the principal directions of deformation can be altered substantially by changing the activation sequence. In conjunction with the observed shearing deformations, particularly near the endocardium, they support the concept that locally the heart wall deforms as a unit with significant transmural tethering.