Most patients with hypertrophic cardiomyopathy (HC) have reduced maximal oxygen consumption (VO2max) during exercise. The degree of impairment is poorly predicted by the magnitude of hypertrophy, left ventricular (LV) outflow tract obstruction, and other conventional markers of disease severity. The aim of this study was to determine the usefulness of N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) as a marker of exercise performance in HC. Plasma NT-pro-BNP was measured in 171 consecutive patients (mean age 46 +/- 18 years) who underwent echocardiography and cardiopulmonary exercise testing. The mean log NT-pro-BNP was 2.79 +/- 0.5; log NT-pro-BNP levels were higher in women patients (p = 0.001) and patients with chest pain (p = 0.010), in New York Heart Association class > or = II (p = 0.009), with atrial fibrillation (p < 0.001), with systolic impairment (p = 0.025), and with LV outflow tract obstructions (p < 0.0001). NT-pro-BNP levels were also correlated with maximal wall thickness (r = 0.335, p < 0.0001), left atrial size (r = 0.206, p = 0.007), and the mitral Doppler E/A ratio (r = 0.197, p = 0.012). The mean percent VO2max achieved was 73.8 +/- 22.6%; percent VO2max was smaller in patients with systolic impairment (p = 0.044) and LV outflow tract obstructions (p = 0.025). There were inverse correlations between percent VO2max and NT-pro-BNP (r = -0.352, p = 0.001), LV end-systolic cavity size (r = -0.182, p = 0.031), and left atrial size (r = -0.251, p = 0.003). On multivariate analysis, only NT-pro-BNP was correlated with percent VO2max. A NT-pro-BNP level of 316 ng/L had 78% sensitivity and 44% specificity (area under the curve 0.616) for predicting percent VO2max < 80%. In conclusion, NT-pro-BNP levels correlate with peak oxygen consumption in HC and are more predictive of functional impairment than other conventional markers of disease severity.