In human plasma samples we compared the values of renin activity, determined with a conventional enzymatic assay, with those of immunoreactive renin, determined with a new, direct immunoradiometric assay which employs highly specific monoclonal antibodies, and with those of angiotensin II; the comparative measurements of renin were carried out also in trypsin activated samples of nephric and anephric subjects. We found that, overall, there was a close relationship between renin activity and immunoreactive renin; however, this relationship was absent when the statistical analysis was restricted to plasmas with low or very low renin. We also found that, within a rather wide range of values, angiotensin II was more closely correlated with immunoreactive renin than with renin activity. Trypsin activation increased to a similar extent immunoreactive renin and renin activity in plasma of nephric and anephric subjects and, overall, the values of total renin obtained with the two assays were significantly correlated. The results of these comparative determinations indicate that, in general, the measurement of immunoreactive renin represents a valid alternative to that of renin activity and a reliable index of the activity of the renin-angiotensin system. In addition, studies with trypsin activation suggest that even in the anephric state human plasma contains an inactive enzyme convertible into an active form which has immunological properties similar to those of active renin.