Transgenic mice displaying abnormalities in cardiac development and function represent a powerful new tool for understanding molecular mechanisms underlying normal cardiovascular function and the pathophysiological bases of human cardiovascular disease. Complete cardiac evaluation of phenotypic changes in mice requires the ability to noninvasively assess cardiovascular structure and function in a serial manner. However, the small mouse heart beating at rates in excess of 500 beats/min presents unique methodological challenges. Two-dimensional and Doppler echocardiography have been recently used as effective, noninvasive tools for murine imaging, because quality images of cardiac structures and valvular flows can be obtained with newer high-frequency transthoracic transducers. We will discuss the use of echocardiography for the assessment of 1) left ventricular (LV) chamber dimensions and wall thicknesses, 2) LV mass, 3) improved endocardial border delineation using contrast echocardiography, 4) LV contractility using ejection phase indices and load-independent indices, 5) vascular properties, and 6) LV diastolic performance. Evaluation of cardiovascular performance in closed chest mice is feasible in a variety of murine models using Doppler echocardiographic imaging. Doppler echocardiography; left ventricular performance GENETIC MODIFICATIONS are frequently used to produce mice models that are used to investigate the molecular basis of cardiac growth and development (7-9, 18, 24, 25) These technologies have led to a proliferation of transgenic and knockout mice models displaying a variety of cardiovascular phenotypes. To evaluate these phenotypes, it is necessary to develop accurate, reproducible, and noninvasive methods to assess cardiac morphology and function in a serial manner.Although it is currently possible to assess cardiac hemodynamics and function using ventricular catheterization, radiolabeled microspheres, and thermodilution techniques in mice, these methods require invasive instrumentation, which restrict the ability to measure physiological changes in a serial manner. Ultrasound imaging has been increasingly applied to identify and characterize structural and functional features of different cardiac phenotypes and pathophysiological responses to surgical and pharmacological interventions in large animal models of human disease (7-9, 16, 17, 27, 43). The small size of the mouse heart, which beats at heart rates in excess of 500 beats/min, presents unique methodological challenges for cardiac ultrasound. Recently developed broadband, phased-array, and linear transducers have small footprints, which are capable of both high frame-rate imaging and improved nearfield imaging, thereby generating high-quality images of the mouse heart.Imaging of the small, fast-beating murine hearts also requires special technical attention to the selection of proper anesthesia. In addition to anesthetic effects, in this review, we will discuss the preparation for image acquisition using currently available echocardiogr...