OBJECTIVE--To study the relation between cardiac systolic activity and cardiac cycle dependent variation in the ultrasound signal arising from within the myocardium. DESIGN--Regional echo amplitude was used as a measure of the myocardial ultrasound signal. Relative echo amplitude values were assigned by standardising echo gain using the posterior parietal pericardium as an in-vivo calibration. M mode measurements of the left ventricle were used to assess cardiac systolic activity. Subjects were studied prospectively. Analysis of echo amplitude was performed by investigators who were blinded to the results of the M mode analysis. The influence of impaired left ventricular performance and abnormal wall motion were assessed. PATIENTS--11 cardiomyopathy patients with impaired ventricular function, eight patients with severe pulmonary hypertension and reversed septal motion, and 19 healthy controls. SETTING--All subject studies were performed at Harefield Hospital. Echo amplitude analysis was performed at the Royal Brompton Hospital. MAIN OUTCOME MEASURES--Cyclic variation in echo amplitude was determined as the change in echo amplitude from end diastole to end systole. Additionally, an index of cyclic variation defined as the ratio of the cyclic change in echo amplitude to end diastolic echo amplitude was measured. Both cyclic variation and the cyclic variation index were analysed to see whether they correlated with left ventricular dimensions, fractional shortening, and systolic wall thickening. RESULTS--Stepwise regression analysis showed systolic wall thickening to be the most significant independent variable that correlated with the cyclic variation index for both the septum and posterior wall (r = 0.68, p = 0.0001, septum; r = 0.69, p = 0.0001, posterior wall). The slopes and intercepts for both regression equations were similar (y = 0.005x + 0.006, septum; y = 0.006x + 0, posterior wall). Subgroup analysis showed that the healthy controls, patients with cardiomyopathy, and patients with pulmonary hypertension had similar slopes and intercepts for their individual regression equations. CONCLUSIONS--These data support the hypothesis of a quantitative relation between the extent of cyclic variation of echo amplitude and the degree of segmental myocardial shortening, as measured by systolic wall thickening, which is not significantly influenced by location within the myocardium, left ventricular performance, or wall motion. They provide further evidence of the usefulness of quantitative analysis of myocardial echo amplitude in the study of regional myocardial function in both normal and injured myocardium.