Light and electron microscopic observations were made on cardiac tissues removed at operation from 91 patients with ventricular hypertrophy, including left ventricular myocardium from 16 patients with aortic valvular disease and from 16 patients with asymmetric septal hypertrophy, and crista supraventricularis muscle from 59 patients with congenital heart diseases associated with right ventricular outflow tract obstruction. In all patients the majority of cardiac muscle cells were hypertrophied, had intact myofibrils, and were surrounded by small amounts of fibrous tissue. In 18 (20%) of the 91 patients cardiac muscle cells with a wide spectrum of degenerative changes were present in addition to hyperthrophied, nondegenerated cells. Early degenerative changes consisted of focal myofibrillar lysis, with preferential loss of thick myofilaments, and focal proliferation of tubules of sarcoplasmic reticulum. Cardiac muscle cells with advanced degeneration had extensive myofibrillar damage and a marked decrease in numbers of myofibrils and T-tubules. The most severely degenerated cells showed selective proliferation of organelles, including sarcoplasmic reticulum, mitochondria, and glycogen, which replaced the contractile elements in the cytoplasm. These findings suggest that degenerated cardiac muscle cells have poor contractile function and may be responsible for impaired cardiac performance in some patients with ventricular hypertrophy. These morphological features appear to represent a final common pathway for degeneration of cardiac muscle cells in a variety of cardiac conditions.