The effects of aging on plasma renin in normotensive volunteers were evaluated by conventional indirect RIA of angiotensin I and a newly developed direct RIA. Plasma renin activity and the plasma concentration of active renin measured by radiometric assay with monoclonal antibody were significantly lower in 14 subjects over 60 years than in 15 subjects under 60 years (plasma renin activity: 0.5 +/- 0.1 vs 1.7 +/- 0.4 nmol.1-1.h-1, P less than 0.01; plasma active renin: 0.50 +/- 0.05 vs 0.87 +/- 0.13 pmol/l, P less than 0.01, means +/- SEM), whereas neither the total renin activity nor the total plasma renin concentration measured by the newly developed immunometric assay were different in the two groups. In another study, the plasma renin concentration, total renin concentration and immunoreactive total renin concentration measured by direct RIA with polyclonal antibody were determined in 17 young (less than 60 years) and 12 elderly (greater than or equal to 60 years) subjects. Plasma renin concentration was significantly lower in the elderly subjects (1.7 +/- 0.2 nmol.l-1.h-1) than in young subjects (3.2 +/- 0.7 nmol.l-1.h-3, P less than 0.05), but the total renin concentration and immunoreactive total renin concentrations in the two groups were not significantly different. These results indicate that the total renin content of the plasma does not change, whereas the active renin content decreases with age in normal subjects, and suggest that activation of prorenin to active renin may be impaired in elderly subjects.