Previous direct measurements of left ventricular systolic wall thickening (SWT) in animal studies have yielded values approximately one-half those found echocardiographically in humans, suggesting a possible overestimation of SWT by echocardiographic techniques. To test the validity of echocardiographic SWT measurements, the relationship between echocardiographically determined end-diastolic and end-systolic left ventricular short-axis myocardial cross-sectional areas (ED Myo CSA and ES Myo CSA, respectively) was assessed in 18 normal subjects. Since Myo CSA is a function of wall thickness and wall circumference, overestimation of SWT by echocardiography would be expected to produce an overestimation of ES Myo CSA relative to ED Myo CSA. SWT, as determined by both M mode (52%) and two-dimensional echocardiography (48%), was consistent with previously reported echocardiographic values, but exceeded that reported in animal studies. By least squares linear regression analysis, ES Myo CSA was 1.078 X ED Myo CSA - 0.385 cm2 (r = .947 SEE = 1.183 cm2) when assessed by one observer and was 1.042 X ED Myo CSA - 0.142 cm2 (r = .906, SEE = 1.831 cm2) when assessed independently by another. The close relationship observed between echocardiographically determined ES Myo CSA and ED Myo CSA was consistent with constant left ventricular myocardial mass throughout the cardiac cycle and thus did not suggest an overestimation of SWT by echocardiographic techniques.