1. The plasma renin concentration (PRC) and active renin concentration determined by radioimmunometric assay (ARC) were measured before and after administration of frusemide or captopril to normal volunteers.
2. Injection of 40 mg of frusemide followed by 1 h in the upright position significantly increased both PRC (P < 0.001) and ARC (P < 0.001). Oral administration of 50 mg of captopril also increased PRC (P < 0.05) and ARC (P < 0.05).
3. ARC and PRC were linearly correlated in the basal supine position [y = 0.635 x − 0.048 (y = PRC, x = ARC), r = 0.958, P < 0.001], after frusemide injection and standing (y = 0.800x + 0.359, r = 0.793,P < 0.02) and after captopril administration in the supine position (y = 0.938x − 0.555, r = 0.998,P < 0.001).
4. A cross-calibration study in which pure human renin was added to pooled plasma and PRC and ARC were measured showed linearity between the values obtained by the two methods.
5. The regression line for values of PRC and ARC in the supine position after captopril administration had a significantly greater slope (P < 0.001) and that for values after frusemide injection and standing was significantly elevated (P < 0.001) compared with the regression line for basal values in the supine position.
6. These results show that the biological activity of renin may be increased by various acute stimulations of renin to inappropriately high levels compared with the immunological activity. This implies that the mode of processing of human plasma renin may be altered by acute stimulation of renin. Furthermore, current methods for assay of plasma active renin may give erroneous values in various pathophysiological conditions.