Left ventricular (LV) mass is an important descriptor of cardiac status that increases with normal aging and may be affected by a variety of disease processes. There are currently limited noninvasive techniques that permit accurate determination of in vivo LV mass in very small animals, such as the mouse, a frequently used model for cardiac research. We sought to evaluate the ability of high-frequency (7.0 or 7.5 MHz), two-dimensional (2-D) guided M-mode echocardiography to estimate in vivo LV mass in the mouse. Fifteen adult mice weighing 22-45 g were studied, including six young adult (2- to 3-mo-old), two adult (12- to 14-mo-old), and seven senescent (18- to 20-mo-old) animals. Resting heart rate varied up to 450 beats/min. Anterior wall, inferior wall, and end-diastolic dimensions were measured, and echocardiographic LV mass (LVMe) was calculated using an uncorrected cube approximation. Autopsy LV mass was determined within 4 h of echocardiographic examination. Autopsy LV mass ranged from 88 to 211 mg. LV chamber dimensions included anterior wall (1.0 +/- 0.2 mm), inferior wall (1.1 +/- 0.3 mm), and end-diastolic dimension (3.7 +/- 0.5 mm). There was a very good correlation between LVMe (x) and autopsy LV mass (y):y = 0.96x - 7, r = 0.94, standard error of the estimate = 18 mg, P < 0.001. This correlation was stronger than that for autopsy LV mass and body weight (r = 0.70) or age (r = 0.74), indexes which until now were the only noninvasive correlates available for this very small animal model. We conclude that, despite the rapid heart rate and small size of the mouse heart, these results demonstrate the potential of high-frequency 2-D guided M-mode transthoracic echocardiography for the in vivo assessment of LV dimensions and mass in the mouse and may prove useful for cardiac research on aging and cardiomyopathies.