This study tested the hypothesis that linear mapping of regional myocardial strain comprehensively assesses variations in regional myocardial function in hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy is characterized by disorganized myocardial architecture that results in spatial and temporal nonuniformity of regional function. Left ventricular deformation was quantified in 20 patients with hypertrophic cardiomyopathy and compared with 25 age- and sex-matched control subjects. Abnormalities in subendocardial strain ranged from reduced longitudinal shortening to paradoxical systolic lengthening and delayed regional longitudinal contractions that were often located in small subsegmental areas. These variations were underestimated significantly by arbitrary measurements compared with linear mapping, in which a region of interest was moved across the longitudinal length of left ventricle (difference of peak and least strain, 10.7% +/- 5.1% vs 17% +/- 5.5%; P < .001). Echocardiographic assessment of variations in regional strain requires careful mapping and may be inappropriately assessed if left ventricular segments are sampled at arbitrary focal locations.