OBJECTIVES: We sought to better understand the effects of aging and gender on left ventricular (LV) structure and function. BACKGROUND: Cardiovascular disease in older persons is associated with increased mortality and morbidity. The influence of gender on age-related cardiac changes is incompletely characterized. METHODS: We studied 34 senescent, male and female, normotensive Fischer rats with transthoracic Doppler echocardiography and morphometric and histopathologic analyses. RESULTS: Male rats were larger (396 +/- 31 g vs. 282 +/- 35 g), and LV mass in males was greater (1.04 +/- 0.22 g vs. 0.67 +/- 0.13 g). However, wall and chamber dimensions normalized to body weight revealed proportionately thicker anterior and posterior walls in females. Relative wall thickness ratio (2 [Diastolic posterior wall thickness]/Diastolic LV internal chamber diameter) was greater in females, but abnormal fractional shortening and diastolic filling (E/A ratio) patterns were more common in males. Significant mitral regurgitation (MR) was sevenfold more common among males (88% vs. 12%, p < 0.001). Histopathologic analysis showed that the cardiac myocytes were larger, and there was greater LV fibrosis in males (both p < 0.001). CONCLUSIONS: Gender-related morphologic and functional differences are important to consider in cardiovascular assessment. Very old rats show significant gender differences in LV size and function. Male rat hearts are larger, thinner and more fibrotic and have indexes of diminished performance. The high prevalence of MR in male rats may play a crucial role in these gender differences.