We determined resting echocardiographic features predictive of latent left ventricular (LV) outflow obstruction in 50 consecutive patients with nonobstructive hypertrophic cardiomyopathy (26 provocable, 24 nonprovocable with amyl nitrite inhalation) to have a better understanding of the pathophysiology of this condition and to identify such patients without pharmacologic provocation. Measurements included wall thickness, type of hypertrophy, LV outflow tract diameter, degree of mitral systolic anterior motion, outflow pressure gradient, and ventricular volume. The direction of the ejection streamline was measured to assess the magnitude of the drag force acting on the mitral valve. Thirteen of 16 patients (81%) with proximal septal bulge were provocable, whereas only 3 of 8 patients (38%) with asymmetric septal hypertrophy and 10 of 26 (38%) with concentric hypertrophy were provocable (p < 0.05). LV outflow tract was significantly narrower and the angle between the ejection flow and the mitral valve was larger in provocable patients. The sensitivity for predicting provocable patients by a combination of a narrow outflow tract (< or = 2 cm) and a large angle (> or = 35 degrees) was 65%, with a specificity of 80% and a positive predictive value of 79%. When these criteria were combined with the presence of septal bulge, the sensitivity was 35%, but the specificity and the positive predictive value were both 100%. Patients with nonobstructive hypertrophic cardiomyopathy with proximal septal bulge, a narrow LV outflow tract, and an oblique angle between the ejection flow and the mitral valve appeared to be predisposed for latent outflow obstruction. These features are consistent with the presence of the large Venturi and drag forces. Thus, the left ventricle, which is capable of increasing both the Venturi and the drog forces on the basis of the morphologic change, contributes to the development of outflow obstruction with amyl nitrite inhalation.