The morphologic determinants of subaortic obstruction in patients with hypertrophic cardiomyopathy are not completely understood. To define the relation between left ventricular outflow tract orifice size and presence or absence of subaortic obstruction, we studied 65 patients with hypertrophic cardiomyopathy and 16 normal controls by quantitative two-dimensional echocardiography. Left ventricular outflow tract area was measured at the onset of systole in the short-axis view in the stop-frame mode. Left ventricular outflow tract area was significantly smaller in patients with hypertrophic cardiomyopathy and subaortic obstruction (2.6 +/- 0.7 cm2) than in patients without obstruction (5.9 +/- 1.6 cm2, p less than 0.001). Twenty of 21 patients with obstruction had a left ventricular outflow tract area smaller than 4.0 cm2, whereas 28 of 30 patients without obstruction had a left ventricular outflow tract area of 4.0 cm2 or greater. The outflow tract area in patients with provocable obstruction (4.6 +/- 1.6 cm2) was intermediate between the areas of patients with and without obstruction. Left ventricular outflow tract area was significantly smaller in patients with hypertrophic cardiomyopathy (4.6 +/- 2.0 cm2) than in normal subjects (10.4 +/- 1.2 cm2, p less than 0.001). We conclude that the cross-sectional outflow tract area is closely related to the presence or absence of subaortic obstruction in patients with hypertrophic cardiomyopathy. Hence, the size of the outflow tract at the level of the mitral valve appears to be of major pathophysiologic significance in producing obstruction in these patients.