The purpose of this study was to examine the regional cardiac mRNA expression and concentration of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in relation to the circulating peptide concentrations in patients with chronic heart failure (CHF). The myocardial mRNA levels and peptide concentrations of BNP and ANP were analysed in seven different regions of the heart from patients undergoing cardiac transplantation. Autopsy samples from individuals without known cardiovascular disease were used as controls. The plasma levels of natriuretic peptides and their N-terminal propeptides, Nt-proBNP and Nt-proANP, were measured in the CHF patients and healthy volunteers. In the autopsy specimens, the atrial regions appeared to contain the highest peptide levels for BNP as well as ANP, the atrioventricular ratio being 12-262 and 72-637-fold, respectively. In the CHF patients there was a relative shift towards the ventricle for BNP, reducing the atrioventricular ratio to 6-16-fold. The circulating concentrations of BNP/Nt-proBNP in the CHF patients correlated closely to the BNP mRNA expression in most myocardial regions including the left ventricle (r = 0.72, P < 0.001). For circulating concentrations of ANP/Nt-proANP, such correlation were limited to the left atrium free wall (r = .66, P < 0.002). Thus, of the two natriuretic peptides, BNP/Nt-proBNP may be a better reflector of left ventricular overload.