A very sensitive and simplified direct radioimmunoassay system for plasma angiotensin II was developed using the antiserum against synthetic angiotensin II (final dilution = 1:1, 500, 000) in combination with ¹²⁵I-labeled angiotensin II (specific activity = 1, 600μCi/μg). In this assay system, it was possible to carry out a direct assay using 100μl of plasma without any extraction procedure. This conclusion was supported by 100% recovery, parallelism of plasma samples against the standard curve, and no difference in hormone levels, there was also a high positive correlation between the plasma angiotensin II levels measured by this direct assay and the dowex column extraction method. The sensitivity of this assay system was 0.1 pg/tube, which is the highest sensitivity in studies reported to date. The cross-reactivities of angiotensin III and I against this antiserum were 100% and less than 0.1%, respectively, suggesting that the antiserum was very specific for the C-terminal of angiotensin II. Plasma angiotensin II levels in normal subjects after overnight fasting ranged from 3.0 to 21.3 pg/ml (12.0±2.1 pg/ml, mean ±SE). By comparison, plasma angiotensin Ii levels of patients with essentiel hypertension were similar to those in the normal renin group, lower than those in low renin group and higher than those in high renin group. In patients with secondary hypertension, levels were lower in those with primary aldosteronism and higher in those with renovascular hypertension when compared to normal subjects.