Sarcolemmal alterations were studied in hypertrophied and/or degenerated ventricular muscle cells from: 1) patients with hypertrophic cardiomyopathy, congestive cardiomyopathy of various causes, aortic valvular disease, or congenital heart diseases associated with obstruction to right ventricular outflow; 2) patients with various neoplasms treated with anthracycline drugs; 3) rabbits given large doses of anthracyclines, and 4) dogs subjected to anoxic cardiac arrest during total cardiopulmonary bypass. Sarcolemmal changes in hypertrophied, nondegenerated cardiac muscle cells consisted of: 1) increase in the area and in the degree of irregularity of cell surfaces, including intercalated discs and T tubules; 2) dilation of T tubules, and 3) formation of large numbers of multiple intercalated discs. Moderately degenerated cardiac muscle cells, with or without associated hypertrophy, showed sarcolemmal changes characterized by: 1) dilation and decreased numbers of T tubules; 2) marked surface irregularity; and 3) dissociation of intercalated discs, associated with development of vesicles in widened disc interspaces, and of variably complex junctional structures formed between two parts of the plasma membrane of the same muscle cell (intracytoplasmic junctions). Sarcolemmal alterations in cells with end-stage degeneration were associated with loss of myofibrils and consisted of: 1) disappearance of T tubules; 2) loss of junctional contacts wtih adjacent cells; 3) marked surface irregularity; 4) formation of intracytoplasmic junctions, and 5) thickening of basement membranes. These observations show that remodeling of the cell surfaces is an important feature of the cellular responses to the stimuli of hypertrophy or degeneration.