Deposition of amyloid in the atria (isolated atrial/cardiac amyloid) is fairly common in the ageing heart. It consists of amyloid fibrils, formed both by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and the precursor molecule of ANP, proANP. This study examines whether amyloidogenic determinants (short peptides/amyloid forming favouring regions) exist in the sequence of NT-proBNP, the N-terminal part of proBNP, and if these determinants form amyloid-like fibrils in vitro. We have predicted a possible amyloidogenic determinant in the sequence of the NT-proBNP and we conclusively show, after its synthesis, that it forms amyloid-like fibrils in-vitro, utilizing transmission electron microscopy, X-ray diffraction, ATR FT-IR and polarizing microscopy. Thus, in this study, a possible biological role is attributed, for the first time, to a certain, specific, part of this important cardiac prohormone/natriuretic peptide, which acts as an important biomarker indicative of heart failure. Its possible direct involvement in isolated cardiac amyloidosis, atrial fibrillation and other types of cardiac amyloidoses is indicated and discussed. Since these cardiac hormones and their prohormones play key roles in cardiovascular homeostasis through natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion (pathophysiology of hypertension and cardiovascular regulation), we also try to suggest these specific, short, peptides as possible future structural targets of efforts towards inhibiting formation of natriuretic peptide(s) amyloid. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2011.