['This paper will describe associations between plasma natriuretic peptide levels and the severity and symptoms of mitral regurgitation (MR).', 'A biochemical test that assisted grading of the severity of MR and the interpretation of symptoms would be of clinical value.', 'Forty-nine patients with isolated MR and left ventricular (LV) ejection fractions (EFs) of >55% underwent transthoracic echocardiography, assessment of symptoms, and measurement of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and its amino-terminal portion, N-BNP.', 'The level of each natriuretic peptide rose with increasing severity of MR and with increases in left atrial (LA) dimensions (p < 0.001 for all comparisons), but no significant correlation existed between any natriuretic peptide and the LV dimensions or EF. Natriuretic peptide levels were higher in symptomatic MR (n = 16, BNP geometric mean 16.9 [95% confidence interval (CI) 13.3 to 21.4] pmol/l) compared with asymptomatic MR (n = 33, BNP 7.1 [95% CI 6.0 to 8.4] pmol/l, p < 0.001), and higher in asymptomatic MR than in normal controls (n = 100, BNP 5.3 [95% CI 4.8 to 5.8] pmol/l, p < 0.0001). These differences were similar for N-BNP and ANP and remained statistically significant (p < 0.05) after adjustment for echocardiographic measures of LV function and severity of MR. Both the sensitivity and the specificity for symptoms for the natriuretic peptides (area under receiver-operator characteristic curve for BNP = 0.90, N-BNP = 0.89, ANP = 0.89) were similar to the MR score (0.88) and greater than for LA dimension (0.81), vena contracta width (0.82), and LV end-systolic dimension (0.63).'] Do plasma natriuretic peptide levels increase with symptoms and severity of mitral regurgitation?