Objective The objective of this study is to determine the effect of nesiritide (human recombinant BNP [hBNP]) in combination with standard therapy on the concentrations of B-type natriuretic peptide (BNP) and N-terminal probrain natriuretic peptide (NT-proBNP). Background B-type natriuretic peptide is synthesized in cardiac ventricles as a prohormone (108 amino acids) and when released into peripheral circulation is cleaved into the active hormone BNP (amino acids 77-108) and an inactive amino terminal fragment NT-proBNP (amino acids 1-76). Methods Three groups of patients with acutely decompensated congestive heart failure (CHF) received nesiritide for 24, 36, or,48 hours (n=5, 7, and 7, respectively) in addition to standard therapy. Serial blood samples were collected. B-type natriuretic peptide and NT-proBNP were measured. Results To correct for positive skew, natriuretic peptide concentrations were log transformed. The mean baseline (prenesiritide), 6-, 12-, and 24-hour infusion, and 6, 12, and 24-hour postinfusion concentrations of BNP were 1000, 2300, 2200, 1700, 580, 640, and 740 pg/mL, respectively (n=19). The 6- and 12-hour postinfusion concentrations of BNP were significantly lower (<0.05) than baseline. The mean baseline, 60-, 120, and 24-hour infusion, and 6-, 12-, and 24-hour postinfusion concentrations of NT-proBNP were 6600, 6500, 5800, 4300, 4100, 4300, and 5100 pg/mL, respectively (n=19). From the time point 24 hours after initiation of therapy through 12 hours postinfusion, the mean NT-proBNP concentration was significantly (<0.05) lower than baseline. Conclusion Nesiritide, in combination with standard therapy, significantly lowered the endogenous concentrations of natriuretic peptides during infusion and after dosing was completed.