Using two radio-immunoassays for N-terminal and C-terminal fragments of human atrial natriuretic polypeptide (ANP) precursor, gamma-hANP [human atrial natriuretic factor-(1-126)], that is gamma-hANP(1-25) [human atrial natriuretic factor-(1-25)] and alpha-hANP [human atrial natriuretic factor-(99-126)], we studied the secretion of gamma-hANP-derived peptides into circulation from the heart in normal subjects and patients with essential hypertension and adrenal disorders. Volume expansion with 2 litres physiological saline increased plasma gamma-hANP(1-25)-like immunoreactivity concomitantly with plasma alpha-hANP-like immunoreactivity in normal subjects. Infusion of angiotensin II (20 ng/kg per min) or noradrenaline (200 ng/kg per min) also caused a parallel increase in plasma gamma-hANP(1-25)-like and alpha-hANP-like immunoreactivity. Plasma gamma-hANP(1-25)-like immunoreactivity levels were changed together with alpha-hANP-like immunoreactivity in patients with essential hypertension and adrenal disorders. These results indicate that gamma-hANP-derived peptides, alpha-hANP and the 10-k N-terminal fragment of gamma-hANP (N-peptide) are cosecreted from the heart and that the simultaneous measurement of N-peptide and alpha-hANP serves as an indicator of the cardiac endocrine function. The significance of N-peptide as a hormone must await further clarification.