Male Sprague-Dawley rats were subjected for 2 weeks to daily injections of homocysteine (Hcy), which increased plasma Hcy approximately 2-fold. Echocardiography indicated significant increases in left ventricular diastolic (13%) and systolic (31%) dimensions and decreases in posterior wall thickness (diastolic, -17%; systolic, -20%) in Hcy-treated animals. Slight changes were noted in the ejection fraction, systolic fractional shortening, and maximal aortic valvular blood flow velocity, but they were not statistically significant or were similar to those in vehicle controls. The results suggest that an initial effect of Hcy administration involves loss of myocardial structure without a direct influence on myocardial contractile function. Consistent with this conclusion, in vitro evaluation of the myocardial ring contractile response showed no significant difference in left ventricular maximal isometric force between the control (13.9 +/- 2.7 g/g tissue) and Hcy-injected (11.0 +/- 2.8 g/g tissue) animals.