To examine the effect of age on the secretion and action of human atrial natriuretic polypeptide (hANP), we compared plasma atrial natriuretic polypeptide and cGMP concentrations in 19 normal young (24-28 yr old) and 31 elderly (64-91 yr old) men. The mean basal plasma hANP level was 25 +/- 5 (+/- SEM) pg/ml in the young men and 120 +/- 22 pg/ml in the elderly men (P less than 0.01). The molecular size of plasma hANP in an aged man was similar to that of alpha hANP. The responses of plasma hANP and cGMP concentrations to an iv infusion of 500 ml 0.15 M NaCl also was compared. Mean plasma hANP concentrations increased significantly in both groups, and the response in the elderly men was exaggerated compared to that in the young men. However, the increases in plasma cGMP concentrations during NaCl loading were similar in both groups. We conclude that 1) the plasma hANP concentrations in healthy elderly men are higher than those in young men, and 2) the higher plasma hANP concentrations may be a compensatory response to reduced hANP activation of its receptors.