Fractional shortening (FS) by echocardiography is considered to represent the short-axis contribution to the stroke volume (SV), also called short-axis function. However, FS is mathematically coupled to the amount of myocardium, since it rearranges during atrioventricular plane displacement (AVPD). The SV is the sum of the volumes generated by 1) reduction in outer volume of the heart, and 2) inner AVPD. The long-axis contribution to the SV is generated by AVPD, and thus the short-axis contribution is the remaining outer volume change of the heart, which should be unrelated to myocardial wall thickness. We hypothesized that both endocardial and midwall shortening indexed to SV are dependent on myocardial wall thickness, whereas epicardial volume change (EVC) indexed to SV is not. Twelve healthy volunteers (normals), 12 athletes, and 12 patients with dilated cardiomyopathy (ejection fraction < 30%) underwent cine cardiac magnetic resonance imaging. Left ventricular long-axis function was measured as the portion of the SV, in milliliters, generated by AVPD. EVC was defined as SV minus long-axis function. Endocardial and midwall shortening were measured in a midventricular short-axis slice. Endocardial shortening/SV and midwall shortening/SV both varied in relation to end-diastolic myocardial wall thickness (R(2) = 0.16, P = 0.008 and R(2) = 0.14, P = 0.012, respectively), whereas EVC/SV did not (R(2) = 0.00, P = 0.37). FS is dependent on myocardial wall thickness, whereas EVC is not and therefore represents true short-axis function. This is not surprising considering that FS is mainly caused by rearrangement of myocardium secondary to long-axis function. FS is therefore not synonymous with short-axis function.