M-mode echocardiographic relative wall thickness (RWT) has been used extensively as an index of left ventricular hypertrophy. To determine whether the more extensive tomographic sampling and enhanced spatial orientation provided by two-dimensional echocardiography (2DE) might improve the value of RWT analysis, we compared 2DE and M-mode RWT in 69 subjects (19 normals, 13 with aortic stenosis, 22 with aortic regurgitation, and 15 with congestive cardiomyopathy). M-mode results correlated relatively weakly with 2DE RWT (r = 0.62 at end diastole; r = 0.81 at end systole). End-systolic M-mode values were larger than 2DE results, while end-diastolic M-mode values were generally smaller than 2DE results (both p less than 0.001). Thus, in congestive cardiomyopathy M-mode RWT was larger than 2DE end-diastolic results and therefore failed to distinguish between cardiomyopathy, aortic regurgitation, and normals. We conclude that M-mode and 2DE analysis of RWT yield disparate results. Moreover, 2DE may enhance the value of RWT in the assessment of left ventricular hypertrophy due to volume overload and cardiomyopathy.