1. Human plasma contains two types of renin: one is active in its native form (active renin), the other has renin-like activity after exposure to low pH (inactive renin). Reactions of acid-activated plasma renin and kidney renin with either homologous or heterologous substrate showed identical Km values.
2. Peripheral venous values for active and inactive renin in essential hypertension (n = 22), renovascular hypertension (n = 14), primary aldosteronism (n = 12), adrenal insufficiency (n = 6) and control subjects (n = 13) were directly correlated. But the percentage of renin that was active varied widely.
3. After bilateral nephrectomy in 12 patients both active and inactive plasma renin fell, but did not completely disappear. Estimates of half-life in two patients were 30–80 min for active renin and 150–165 min for inactive renin.
4. Renal vein to peripheral vein ratios of active and inactive renin in ten patients with essential hypertension (19 determinations) ranged from 0·96 to 1·60 and from 0·68 to 1·44 respectively with mean values (±sem) of 1·21 ± 0·04 and 1·06 ± 0·05.
5. The renal vein to peripheral vein ratio of active renin on the affected side in 13 out of 17 patients with renovascular hypertension was above the range found in essential hypertension. Six of them also had an elevated ratio of inactive renin on that side, which indicated renal release of this form of renin into the circulation. But, in contrast to the renal vein to peripheral vein ratio of active renin, the mean value of the ratio of inactive renin on the affected side was not significantly higher than on the contralateral side. The results suggest a renal mechanism not only for controlling the total quantity of circulating renin but also for modulating its degree of activation.