Histologic analysis of biopsies derived from patients with chronic dysfunctional but viable (hibernating) myocardium showed characteristic cell alterations. These changes consisted of a partial to complete loss of sarcomeres, accumulation of glycogen, and disorganization and loss of sarcoplasmic reticulum. Most of the adaptive changes that these affected cells undergo are suggestive of dedifferentiation. In the present study the expression and organizational pattern of contractile and cytoskeletal proteins such as titin, cardiotin, and α-smooth muscle actin were assessed in hibernating and normal myocardium because the expression and organization of these constituents have been related to certain stages of cardiomyocyte differentiation. In normal cells titin shows a cross-striated staining pattern, whereas cardiotin displays a fibrillar array, parallel to the sarcomeres. α-Smooth muscle actin is not expressed in adult cardiomyocytes. The expression of titin in a punctated pattern and the marked decrease to virtual absence of cardiotin in hibernating cardiomyocytes speak in favor of an embryonic phenotype of these cells. The re-expression of α-smooth muscle actin in hibernating cells strongly supports this hypothesis. The observations on three different structural proteins of heart muscle suggest that hibernating myocardium acquired aspects of muscle cell dedifferentiation.