Adults with nonrestrictive ventricular septal defects have chronic hypoxemia that may lead to alterations in myocardial structure and function. Ultrasonic integrated backscatter provides quantitative assessment of myocardial acoustic properties that are altered by myocardial ischemia, fibrosis, and edema. Sixteen patients (age 31 +/- 10 years) with a nonrestrictive ventricular septal defect were studied using 2-dimensional and M-mode echocardiography with integrated backscatter imaging to determine the cyclic variation of integrated backscatter in the right ventricular free wall, ventricular septum, and left ventricular posterior wall. Cyclic variation of integrated backscatter in the right ventricular free wall and interventricular septum in patients was significantly less than that in control subjects (4.1 +/- 0.8 vs 4.9 +/- 1.0 decibels [dB], p = 0.02, and 3.8 +/- 1.2 vs 4.8 +/- 1.1 dB, p = 0.004, respectively). There was no difference between mean cyclic variation of integrated backscatter in the left ventricular posterior wall in patients and that in control subjects (4.7 +/- 1.3 vs 4.8 +/- 1.1 dB, p = NS, respectively). However, values < 4.0 dB were noted in 38% of patients compared with 15% of control subjects. Biventricular systolic function was normal in all but 1 patient. There was no correlation between backscatter and either wall thickness or percent wall thickening from the 3 regions. Histologic analysis of myocardial tissue in 3 patients revealed interstitial and replacement fibrosis. Adults with nonrestrictive ventricular septal defects exhibit alterations in tissue-acoustic properties detectable by integrated backscatter imaging despite preserved systolic function and wall thickening.