Light microscopic and ultrastructural observations were made on left atrial tissues obtained from 14 patients at the time of operation for correction of mitral valvular disease. Cardiac muscle cells varied in size but most frequently were hypertrophied. In fibrotic areas, present in all left atria, the muscle cells tended to be isolated from adjacent cells and exhibited degenerative changes of varying severity. These changes consisted or proliferation of Z-band material and cytoskeletal filaments, myofibrillar loss, proliferation of elements of free and extended junctional sarcoplasmic reticulum, variations in size and number of mitochondria, occurrence of abnormal mitochondria, dissociation of intercellular junctions, formation of spherical microparticles, and accumulation of lysosomal degradation products. Hypertrophy was considered to lead to cellular degeneration, with decrease or loss of contractile function. Atrial fibrillation was associated with severe cellular degeneration. The severity of degeneration was greater in patients with mitral regurgitation, with or without associated mitral stenosis, than in patients with pure mitral stenosis.