Congestive heart failure is accompanied by increased cardiac brain natriuretic peptide (BNP) gene expression with elevated plasma concentrations of BNP and its precursor, proBNP. We investigated if myocardial ischemia in the absence of overt heart failure may be another mechanism for increased myocardial BNP expression. The BNP expression was examined in hypoxic myocardium of patients undergoing coronary bypass grafting surgery, in patients with coronary artery disease and normal left ventricular function undergoing percutaneous transluminal intervention therapy, and in heart failure patients without coronary artery disease. BNP mRNA was quantified by real-time PCR, and plasma BNP and proBNP concentrations were measured with radioimmunoassays. Quantitative analysis of BNP mRNA in atrial and ventricular biopsies from coronary bypass grafting patients revealed close associations of plasma BNP and proBNP concentrations to ventricular, but not atrial, BNP mRNA levels. Plasma BNP and proBNP concentrations were markedly increased in patients with coronary artery disease but without concomitant left ventricular dysfunction. These results are compatible with the notion that myocardial ischemia, even in the absence of left ventricular dysfunction, augments cardiac BNP gene expression and increases plasma BNP and proBNP concentrations. Thus, elevated BNP and proBNP concentrations do not necessarily reflect heart failure but may also result from cardiac ischemia.