Acute right ventricular pressure overload shifts the interventricular septum leftward and decreases systolic shortening of the left ventricular (LV) septal-lateral diameter. These changes should alter regional shortening in the LV minor axis. To test this hypothesis, LV minor axis circumferential segment lengths of the septum and anterior, lateral, and posterior walls were measured during pulmonary artery or venae caval constriction in seven open-chest dogs with intact pericardia. Starting at an end-diastolic pressure of 10 mm Hg, venae caval constriction decreased LV end-systolic pressure by 19 ± 6% and stroke volume by 40 ± 15% and produced uniform decreases in systolic shortening and end-diastolic length around the minor axis. However, during pulmonary artery constriction resulting in similar decreases in end-systolic pressure (22 ± 7%) and stroke volume (39 ± 11%), decreases in systolic shortening were significantly larger in the anterior (−34 ± 10%) and posterior (−33 ± 21%) walls than in the septum (−10 ± 9%) or lateral wall (−8 ± 13%). The mechanisms of these large anterior and posterior shortening decreases differed: anterior end-diastolic length decreased more than posterior and lateral end-diastolic lengths, while posterior end-systolic length decreased less than anterior and lateral end-systolic lengths. Similar changes were seen at starting enddiastolic pressures of 5 and 15 mm Hg. Propranolol did not alter this nonuniform response, while pericardiectomy attenuated the regional variations. Thus, changes in LV geometry during acute right ventricular pressure overload are associated with nonuniform regional changes in systolic shortening in the LV minor axis that are enhanced by the pericardium.