Natriuretic peptides control cardiovascular functions through diuretic, natriuretic, and vasodilatory properties. Several anthropometric, cardiac and renal variables were found to be independently correlated to their levels. Few studies, however, systematically investigated the independent determinants of natriuretic peptide levels in large populations. The present analysis was carried out in a large unselected sample of adult male population in Southern Italy (The Olivetti Heart Study, n = 806 men, mean age = 59.5, range 35-82 years). We examined the relationship of plasma natriuretic peptide-proatrial natriuretic peptide (NT-proANP) levels with relevant anthropometric, clinical and biochemical variables; the impact of age; and the association of NT-proANP levels with cardiovascular risk. NT-proANP was directly associated to age, pulse pressure (PP), renal sodium fractional excretion (FENa) (P < 0.005), and inversely to diastolic blood pressure (DBP), heart rate (HR), creatinine clearance, body mass index (BMI), arm and leg circumferences (P < 0.005). After adjustment for age, DBP, creatinine clearance, FENa and HR remained independent determinants of NT-proANP levels (all P < 0.01, cumulative R = 0.186). Upon stratification of our population by tertile of age, NT-proANP was significantly associated (P