We have shown previously that the physical properties of myocardium in dogs can be characterized with quantitative ultrasonic integrated backscatter and that interrogation of the tissue with ultrasound can delineate cardiac cycle-dependent changes in ultrasonic backscatter in normal tissue that disappear with ischemia and reappear with reperfusion if functional integrity is restorable. To determine whether this approach can be applied to man, we implemented an automatic gain compensation and continuous data acquisition system to characterize myocardium with quantitative ultrasonic backscatter and to detect cardiac cycle-dependent changes in real time. We developed a two-dimensional echocardiographic system with quantitative integrated backscatter imaging capabilities for use in human subjects that can automatically differentiate ultrasonic signals from blood as opposed to those obtained from tissue and adjust the slope of the gain compensation appropriately. Real-time images were formed from a continuous signal proportional to the logarithm of the integrated backscatter along each A-line. In our initial investigation, 15 normal volunteers (ages 17 to 40 years, heart rates 44 to 88 beats/min) and five patients with dilated cardiomyopathy (ages 22 to 52, heart rates 82 to 120 beats/min) were studied with conventional parasternal long-axis echocardiographic views. Diastolic-to-systolic variation of integrated backscatter in the interventricular septum and left ventricular posterior wall was seen in each of the normal subjects averaging 4.6 ± 1.4 dB (SD) and 5.3 ± 1.5 dB (n = 127 sites), respectively. In patients with dilated cardiomyopathy, the magnitude of this variation was either reduced or absent, averaging 0.9 ± 0.8 dB in the interventricular septum and 1.8 ± 1.2 dB in the left ventricular posterior wall (n = 31 sites; p < .01 for both). In eight of the 31 sites in myopathic hearts, no variation was detectable. The results obtained demonstrate that quantitative ultrasonic tissue characterization is feasible in man. Real-time integrated backscatter imaging delineates cardiac cycle-dependent changes in normal human myocardium and quantitatively differentiates between normal and myopathic myocardium. This system offers promise for the quantitative, diagnostic detection of diverse disease processes, including myocardial ischemia and responses of the tissue to reperfusion.