Because ventricular wall tension is related to wall curvature by the Laplace law, the curvature should affect regional wall function. We hypothesized that the ineffective (isometric) contraction of the interventricular septum observed in hypertrophic cardiomyopathy (HCM) may be related to its abnormal curvature. To address this issue, we studied 17 HCM patients with various septal morphologies and normal overall systolic function (mean echocardiographic fractional shortening, 48 ± 9%) using MRI tagging (spatial modulation of magnetization); there was asymmetric septal hypertrophy, prominent basal septal bulge and concentric hypertrophy in 7, 4, and 6 patients, respectively. Localized endocardial (endo %S) and epicardial (epi %S) intra-myocardial circumferential shortening was measured in the septal and lateral walls on a basal short-axis slice. Short-axis curvature (SXC) and long-axis curvature (LXC) of the basal septal and basal lateral walls were determined as the reciprocal of the radius of the arc best fit to the wall curvature, which can be negative if the wall is convex to the LV cavity. Wall thickness was also measured at end-diastole. Endo %S and epi %S were significantly lower in the septum than in the lateral wall, suggesting isometric septal contraction (20 ± 14 vs 45 ± 11%, P < 0.0001 for endo %S and 10 ± 9 vs 20 ± 11%, p < 0.001 for epi %S). Septal walls were flatter in the short axis plane and more convex toward the LV cavity in the long-axis plane than lateral walls as indicated by smaller SXC and LXC (0.08 ± 0.03 vs 0.11 ± 0.03 mm -1 for SXC, -0.02 ± 0.02 vs 0.03 ± 0.01 mm -1 for LXC both p < 0.0001). There were significant correlations between %S and curvature and thickness as follows. septal wall lateral wall endo %S epi%S endo %S epi%S SXC NS NS NS r = 0.57 LXC r = 0.56 r = 0.62 r = 0.55 NS thickness r = -0.63 r = -0.49 NS NS Multiple stepwise linear regression analysis showed that both wall thickness and LXC significantly contributed to %S in the septum (r = 0.79 for endo %S, r = 0.74 for epi %S, both p < 0.005). 1) Wall thickness and long-axis curvature appear to predict the septal function, whereas they have little impact on lateral wall function. 2) The thicker and more convex (toward the ventricular cavity) the septum is, the less it thickens in systole. 3) Isometric contraction of the interventricular septum in HCM may be partly due to its abnormal curvature.