ABSTRACTUsing nondenaturing polyacrylamide gel electrophoresis, we have identified two distinct myosin isoenzymes in human atrial tissue that correspond to the V1 and V3 isomyosins found in rat ventricular tissue. Normal left and right atrial appendages have approximately 50% V3. When the left atrium was exposed to hemodynamic overload secondary to mitral stenosis, the percent V3 increased to 77 + 10% (n = 10); exposure to hemodynamic overload secondary to mitral regurgitation caused an increase to 70 14% (n = 6). Changes in the isoenzyme pattern were seen in the right atria of patients with mitral stenosis and markedly elevated pulmonary arterial pressures compared with control subjects and patients with mitral stenosis without severe pulmonary hypertension. Several clinical variables were examined to determine which factors might influence isoenzyme expression. Age, sex, the presence of atrial fibrillation, and pulmonary capillary wedge pressure did not predict the isoenzyme pattern. However, patients with mitral valvular disease and only slightly enlarged left atria tended to have a higher percent V3 than those with massively enlarged atria. These data confirm that human atrial tissue, like rat ventricular tissue, can alter its isomyosin composition in response to a hemodynamic load. The data further suggest that the isoenzyme shift is an early adaptation to the imposed load.