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Brain natriuretic peptide (BNP) is important in the diagnosis and management of heart failure (HF). Sometimes, very high BNP levels encountered in clinical settings seem to be out of proportion to the severity of HF. The authors retrospectively identified 113 patients with 129 admissions with a BNP value >3000 pg/mL regardless of diagnosis. The data set was analyzed using the Student t test and bivariate analysis. Fewer than half of patients were admitted for HF. In 14 patients (10.9%), no signs of HF were found. The BNP level of those with and without HF was similar. There was no difference in BNP level in patients with and without systolic dysfunction or renal dysfunction and between different age groups. Extreme values of BNP do not necessarily correlate with the presence of HF, cardiomyopathy, or kidney dysfunction. When the magnitude of BNP elevation is very high, its clinical significance is limited. Congest Heart Fail. 2010;16:221–225. © 2010 Wiley Periodicals, Inc.