Progress in tissue characterization of myocardium with ultrasound suggests that quantitative recognition of ischemic or scarred tissue will be achieved. Despite the increasing recognition and importance of cardiomyopathy, its diagnosis generally requires invasive procedures such as cardiac catheterization and biopsy. To investigate methods that permit the characterization of longitudinal cardiomyopathic changes that might ultimately be extended for noninvasive studies in patients, quantitative ultrasonic methods were utilized for in vitro tissue characterization of hearts from Syrian hamsters of selected age of either 2 to 3 or 5 to 7 months. Normal hamsters were used as controls. Myocardial sites (n = 600) from the young Syrian hamsters exhibited values (± standard error) of integrated ultrasonic backscatter averaging −53.87 ± 0.26 dB, which were significantly different from values (n = 500) in age-matched control hamsters (−58.07 ± 0.08 dB; p < 0.001). Cardiomyopathic hearts from older animals exhibited backscatter values (n = 500 sites) averaging −50.87 ± 0.22 dB, again significantly different from values (n = 300 sites) in age-matched control hamsters (−55.91 ± 0.11 dB; p < 0.001). In addition, ultrasonic attenuation was significantly different for hearts from the control and cardiomyopathic hamsters of both age ranges. The results correlated with sequential calcification and fibrosis characteristics assessed histopathologically. This study indicates that quantitative characterization of myocardium with ultrasound may permit longitudinal assessment of cardiomyopathic changes in diverse disease entities and their response to therapy.