ABSTRACTAnalyses of regional left ventricular systolic wall motion or thickening overestimate infarct size. We used quantitative two-dimensional echocardiographic analysis of systolic thickening and contrast two-dimensional echocardiography to evaluate causes for that overestimation. The following possibilities were considered: (1) “tethering,” defined as dysfunction of contrast-enhancing myocardium adjacent to ischemic or contrast-negative regions, and (2) the role of standard center of mass analysis algorithms, which may overestimate wall motion abnormalities because of the axis shift produced by simultaneous systolic expansion of the ischemic segment and systolic contraction of the nonischemic segment. In the short-axis view in 12 animals, the echo contrast defect (ECD) occupied 32 + 7% of the left ventricular circumference. Extent of dysfunction by the center of mass analysis was 39 + 5% of the left ventricular circumference and correlation with ECD size was .68 (SEE = 5.2%). Thus 8 -+- 6% of the circumference of the left ventricle was assessed to be dysfunctional yet enhanced with contrast. Tethering accounted for only half of this (4 + 4% of left ventricular circumference) and involved less than 1 cm on either side of the ECD. The remaining overestimation by the center of mass analysis correlated significantly (r = .89, p < .01) with the amount of systolic expansion of the ECD. This expansion of the ECD (increase in angle subtended by the ECD of 11 ± 8%) was produced by the systolic shift in the center of mass toward the dysfunctional segment from contraction of the opposite, nonischemic segment, since true systolic lengthening of the ischemic (contrast-negative) segment wasminimal (increase of only 3 + 5%; p < .01 vs increase in angle subtended by ECD). When systolic function was analyzed independent of a center of mass with the ECD as an internal reference, the correlation between extent of dysfunction and ECD size improved to .84 (SEE = 3.8%). In conclusion, two-dimensional echocardiography has exaggerated the importance of tethering because of flaws in standard analysis algorithms. Tethering does lead to an unavoidable overestimation of infarct size, but the amount of myocardium involved is small and relatively predictable. The remainder of the overestimation of infarct size by two-dimensional echocardiography is critically dependent on systolic function of the opposite, nonischemic wall. Since this is variable, it accounts in large part for the suboptimal correlation between infarct size and extent of dysfunction by standard two-dimensional echocardiographic analyses.